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1. Mutation of SPINOPHILIN (PPP1R9B) found in human tumors promotes the tumorigenic and stemness properties of cells

Author

Daniel Otero-Albiol, Sandra Muñoz-Galván, Eva M. Verdugo-Sivianes, Amancio Carnero, Ana M. Rojas, [Verdugo-Sivianes,EM, Muñoz-Galván,S, Otero-Albiol,D, Carnero,AS] Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocio, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Spain. [Verdugo-Sivianes,EM, Carnero,AS] CIBERONC, Instituto de Salud Carlos III, Madrid, Spain. [Rojas,AM] Centro Andaluz de Biología del Desarrollo (CABD), CSIC-Universidad Pablo de Olavide, Sevilla, Spain., This work was supported by grants from the Ministerio de Ciencia, Innovación y Universidades (MCIU) Plan Estatal de I+D+I 2018, a la Agencia Estatal de Investigación (AEI) y al Fondo Europeo de Desarrollo Regional (MCIU/AEI/FEDER, UE): RTI2018-097455-B-I00 and RTI2018-096735-B-I00grant from AEI-MICIU/FEDER (RED2018-102723-T), from CIBER de Cáncer (CB16/12/00275), co-funded by FEDER from Regional Development European Funds (European Union), from Consejeria de Salud (PI-0397-2017) and Consejeria of Economía, Conocimiento, Empresas y Universidad of the Junta de Andalucia (P18-RT-2501). Special thanks are also due to the Fundacion AECC and Fundacion Eugenio Rodriguez Pascual for supporting this work., Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Centro de Investigación Biomédica en Red Cáncer (España), Junta de Andalucía, Fundación Científica Asociación Española Contra el Cáncer, and Fundación Eugenio Rodríguez Pascual

Subjects
0301 basic medicine, Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor [Medical Subject Headings], Proteína de retinoblastoma, Carcinogenesis, Mutant, Medicine (miscellaneous), Anatomy::Cells::Stem Cells::Neoplastic Stem Cells [Medical Subject Headings], medicine.disease_cause, environment and public health, Retinoblastoma Protein, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Mice, 0302 clinical medicine, Breast cancer, pRB, Anatomy::Cells::Cells, Cultured::Cell Line [Medical Subject Headings], stem cell phenotype, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nerve Tissue Proteins [Medical Subject Headings], Protein Phosphatase 1, Organisms::Eukaryota::Animals [Medical Subject Headings], Proteína fosfatasa 1, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Drug Evaluation, Preclinical::Drug Screening Assays, Antitumor::Xenograft Model Antitumor Assays [Medical Subject Headings], Phosphorylation, Phenomena and Processes::Metabolic Phenomena::Metabolism::Phosphorylation [Medical Subject Headings], Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Cycle [Medical Subject Headings], Cell Line, Transformed, Mutation, Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Microfilament Proteins [Medical Subject Headings], Retinoblastoma, Línea celular, Microfilament Proteins, Proteína 1 de unión a retinoblastoma, Cell cycle, Diseases::Neoplasms::Neoplastic Processes::Carcinogenesis [Medical Subject Headings], PP1, Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Cycle::Cell Cycle Checkpoints::G1 Phase Cell Cycle Checkpoints [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Tumor Suppressor Proteins::Tumor Suppressor Protein p53 [Medical Subject Headings], Gene Expression Regulation, Neoplastic, Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Transformed [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Eye Neoplasms::Retinal Neoplasms [Medical Subject Headings], SPINOPHILIN, 030220 oncology & carcinogenesis, Neoplasias de la mama, Neoplastic Stem Cells, Cell lines, Female, biological phenomena, cell phenomena, and immunity, Research Paper, Signal Transduction, Carcinogénesis, cancer stem cell, animal structures, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], Stem cell phenotype, Mice, Nude, Breast Neoplasms, Nerve Tissue Proteins, macromolecular substances, Biology, Resting Phase, Cell Cycle, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Tumor Suppressor Proteins::Retinoblastoma Protein [Medical Subject Headings], Dephosphorylation, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Phosphoric Monoester Hydrolases::Phosphoprotein Phosphatases::Protein Phosphatase 1 [Medical Subject Headings], 03 medical and health sciences, Cancer stem cell, Cell Line, Tumor, medicine, Animals, Humans, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Células madre neoplásicas, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings], Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal Transduction [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, Nude [Medical Subject Headings], pocket proteins, medicine.disease, G1 Phase Cell Cycle Checkpoints, Xenograft Model Antitumor Assays, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Neoplastic [Medical Subject Headings], enzymes and coenzymes (carbohydrates), tumorigenesis, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Tumor progression, Cell culture, Retinoblastoma protein, Tumorigenesis, Cancer research, Tumor Suppressor Protein p53, Pocket proteins, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Holoenzymes [Medical Subject Headings]
Abstract

[Rationale] SPINOPHILIN (SPN, PPP1R9B) is an important tumor suppressor involved in the progression and malignancy of different tumors depending on its association with protein phosphatase 1 (PP1) and the ability of the PP1-SPN holoenzyme to dephosphorylate retinoblastoma (pRB)., [Methods] We performed a mutational analysis of SPN in human tumors, focusing on the region of interaction with PP1 and pRB. We explored the effect of the SPN-A566V mutation in an immortalized non-tumorigenic cell line of epithelial breast tissue, MCF10A, and in two different p53-mutated breast cancer cells lines, T47D and MDA-MB-468., [Results] We characterized an oncogenic mutation of SPN found in human tumor samples, SPN-A566V, that affects both the SPN-PP1 interaction and its phosphatase activity. The SPN-A566V mutation does not affect the interaction of the PP1-SPN holoenzyme with pocket proteins pRB, p107 and p130, but it affects its ability to dephosphorylate them during G0/G1 and G1, indicating that the PP1-SPN holoenzyme regulates cell cycle progression. SPN-A566V also promoted stemness, establishing a connection between the cell cycle and stem cell biology via pocket proteins and PP1-SPN regulation. However, only cells with both SPN-A566V and mutant p53 have increased tumorigenic and stemness properties., [Conclusions] SPN-A566V, or other equivalent mutations, could be late events that promote tumor progression by increasing the CSC pool and, eventually, the malignant behavior of the tumor., This work was supported by grants from the Ministerio de Ciencia, Innovación y Universidades (MCIU) Plan Estatal de I+D+I 2018, a la Agencia Estatal de Investigación (AEI) y al Fondo Europeo de Desarrollo Regional (MCIU/AEI/FEDER, UE): RTI2018-097455-B-I00 and RTI2018-096735-B-I00 grant from AEI-MICIU/FEDER (RED2018-102723-T); from CIBER de Cáncer (CB16/12/00275), co-funded by FEDER from Regional Development European Funds (European Union); from Consejeria de Salud (PI-0397-2017) and Consejeria of Economía, Conocimiento, Empresas y Universidad of the Junta de Andalucia (P18-RT-2501). Special thanks are also due to the Fundacion AECC and Fundacion Eugenio Rodriguez Pascual for supporting this work.

Published
2021

2. Evidence Update on the Relationship between Diet and the Most Common Cancers from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study: A Systematic Review

Author

Ubago-Guisado, Esther, Rodríguez-Barranco, Miguel, Ching-López, Ana, Petrova, Dafina, Molina-Montes, Esther, Amiano, Pilar, Barricarte-Gurrea, Aurelio, Chirlaque, María-Dolores, Agudo, Antonio, Sánchez, María-José, [Ubago-Guisado,E, Rodríguez-Barranco,M, Ching-López,A, Petrova,D, Sánchez,MJ] Cancer Registry of Granada, Escuela Andaluza de Salud Pública, Granada, Spain. [Ubago-Guisado,E, Molina-Montes,E, Amiano,P, Barricarte-Gurrea,A, Chirlaque,MD, Sánchez,MJ] Epidemiology and Control of Chronic Diseases, CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Ubago-Guisado,E, Sánchez,MJ] Cancer Epidemiology Group, Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Petrova,D] Department of Experimental Psychology, Mind, Brain and Behavior Research Center (CIMCYC), University of Granada, Granada, Spain. [Molina-Montes,E] Department of Nutrition and Food Science, Campus of Cartuja, University of Granada, Granada, Spain. [Molina-Montes,E] Institute of Nutrition and Food Technology (INYTA) ‘José Mataix’, Biomedical Research Centre, University of Granada, Granada, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, Spain. [Barricarte-Gurrea,A] Navarra Public Health Institute, Pamplona, Spain. [Barricarte-Gurrea,A] Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Chirlaque,MD] Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain. [Agudo,A] Unit of Nutrition and Cancer, Catalan Institute of Oncology, L’Hospitalet de Llobregat, Spain. [Agudo,A] Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute—IDIBELL, L’Hospitalet de Llobregat, Spain. [Sánchez,MJ] Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain., and E.U.-G. is supported by the Programa Operativo Fondo Social Europeo (FSE) de Andalucía (2014–2020) and Junta de Andalucía (reference DOC_01618).

Subjects
Metaanalisis, Frutas, Meat, Neoplasias de la próstata, Neoplasias pulmonares, Etanol, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms [Medical Subject Headings], Carne, Fruits, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Ingestión de alimentos, Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms [Medical Subject Headings], Breast cancer, Neoplasias colorrectales, Vegetables, Prospective Studies, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Prostate cancer, Revisión sistemática, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Diseases::Neoplasms [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena [Medical Subject Headings], Colorectal cancer, Fish, Verduras, Neoplasias de la mama, Intake, Geographical Locations::Geographic Locations::Europe [Medical Subject Headings], Lung cancer, Alcohol
Abstract

The European Prospective Investigation into Cancer and Nutrition (EPIC) is a multicentre prospective study conducted in 23 centres in 10 European countries. Here we review the findings from EPIC on the relationship between diet-related exposures and incidence or mortality from the four most frequent cancers in the European population: colorectal, breast, lung, and prostate cancer. We conducted a systematic review following PRISMA guidelines and identified 110 high-quality studies based on the EPIC cohort. Fruit and vegetable consumption had a protective effect against colorectal, breast, and lung cancer, whereas only fruit had a protective effect against prostate cancer. A higher consumption of fish and lower consumption of red and processed meat were related with a lower risk of colorectal cancer; and higher consumption of fatty fish with lower risk of breast cancer. Calcium and yogurt intake were found to protect against colorectal and prostate cancer. Alcohol consumption increased the risk for colorectal and breast cancer. Finally, adherence to the Mediterranean diet emerged as a protective factor for colorectal and breast cancer. The EPIC study results are in agreement with the latest evidence from leading authorities on cancer prevention and help to inform public prevention policies and strategies. Yes

Published
2021

3. Metalloproteinases 1 and 3 as Potential Biomarkers in Breast Cancer Development

Author

Amanda Rocío González Ramírez, Sandra Ríos Arrabal, Pablo Torne Poyatos, Alejandro Alonso, Angela Ximena Argote Camacho, María Auxiliadora Olivares Urbano, Juan David Rejón García, María Isabel Núñez, [Argote Camacho,AX] Department of Surgery, Clínico San Cecilio University Hospital, Granada, Spain. [González Ramírez,AR] Bio-Health Research Foundation of Eastern Andalusia—Alejandro Otero (FIBAO), Granada, Spain. [Pérez Alonso,AJ] Department of Surgery, Virgen de las Nieves University Hospital, Granada, Spain. [Rejón García,JD] Andalusian Tumour Bank Network, Granada, Spain. [Olivares Urbano,MA, Ríos Arrabal,S, Nuñez,MI] Department of Radiology and Physical Medicine, University of Granada, Granada, Spain. [Torné Poyatos,P] Department of Surgery and Its Specialties, University of Granada, Granada, Spain. [Nuñez,MI] Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada, Spain. [Nuñez,MI] Biosanitary Research Institute, ibs.Granada, Granada, Spain., and This research was funded by Fundación Progreso Salud, grant number PI-0730-2013, and by ISCIII, grant number PIE16/00045.

Subjects
Oncology, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Endopeptidases::Metalloendopeptidases::Collagenases::Matrix Metalloproteinase 2 [Medical Subject Headings], Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Metalloproteases [Medical Subject Headings], Metaloproteinasas de la matriz, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], Disease, Matrix metalloproteinase, medicine.disease_cause, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Endopeptidases::Metalloendopeptidases::Collagenases::Matrix Metalloproteinase 1 [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Endopeptidases::Metalloendopeptidases::Matrix Metalloproteinases::Matrix Metalloproteinases, Secreted::Matrix Metalloproteinase 3 [Medical Subject Headings], MMP inhibitors, Medicine, Breast, Biology (General), Spectroscopy, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Aged, 80 and over, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Metalloproteases::Metalloendopeptidases::Collagenases::Matrix Metalloproteinase 9 [Medical Subject Headings], Mortality rate, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Proteinase Inhibitory Proteins, Secretory::Tissue Inhibitor of Metalloproteinases [Medical Subject Headings], Proteolytic enzymes, Tissue Inhibitor of Metalloproteinases, General Medicine, Diseases::Neoplasms::Neoplastic Processes::Carcinogenesis::Cocarcinogenesis [Medical Subject Headings], Middle Aged, Immunohistochemistry, Computer Science Applications, Chemistry, Matrix Metalloproteinase 9, Disease Progression, Matrix Metalloproteinase 2, Female, Matrix Metalloproteinase 3, Matriz extracelular, MMPs, Matrix Metalloproteinase 1, Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, Pharmacological [Medical Subject Headings], medicine.medical_specialty, QH301-705.5, extracellular matrix, Breast Neoplasms, Catalysis, Article, metalloproteinases, Inorganic Chemistry, Breast cancer, breast cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Internal medicine, Biomarkers, Tumor, Humans, Metaloproteasas, immunohistochemical expression, Physical and Theoretical Chemistry, Molecular Biology, QD1-999, Linfedema del cáncer de mama, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Retrospective Studies, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Progression [Medical Subject Headings], business.industry, Organic Chemistry, Inhibidores de la metaloproteinasa de la matriz, biomarkers, Retrospective cohort study, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], medicine.disease, Biomarcadores, Persons::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings], Spain, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], diagnostic factors, Case-Control Studies, Metalloproteases, business, Carcinogenesis, epithelial-to-mesenchymal transition (EMT)
Abstract

Breast cancer continues to be one of the main causes of morbidity and mortality globally and was the leading cause of cancer death in women in Spain in 2020. Early diagnosis is one of the most effective methods to lower the incidence and mortality rates of breast cancer. The human metalloproteinases (MMP) mainly function as proteolytic enzymes degrading the extracellular matrix and plays important roles in most steps of breast tumorigenesis. This retrospective cohort study shows the immunohistochemical expression levels of MMP-1, MMP-2, MMP-3, and MMP-9 in 154 women with breast cancer and 42 women without tumor disease. The samples of breast tissue are assessed using several tissue matrices (TMA). The percentages of staining (≤50%–&gt, 50%) and intensity levels of staining (weak, moderate, or intense) are considered. The immunohistochemical expression of the MMP-1-intensity (p = 0.043) and MMP-3 percentage (p = 0.018) and intensity, (p = 0.025) present statistically significant associations with the variable group (control–case), therefore, expression in the tumor tissue samples of these MMPs may be related to the development of breast cancer. The relationships between these MMPs and some clinicopathological factors in breast cancer are also evaluated but no correlation is found. These results suggest the use of MMP-1 and MMP-3 as potential biomarkers of breast cancer diagnosis.

Published
2021

4. Bisphenol-A exposure and risk of breast and prostate cancer in the Spanish European Prospective Investigation into Cancer and Nutrition study

Author

Sandra Colorado, María José Sánchez, Ana Jimenez, Antonio Agudo, Pilar Amiano, Elena Salamanca-Fernández, Marcela Guevara, Nicolás Olea, Fernando Vela, Josu Delfrade, Juan P. Arrebola, Miguel Rodríguez-Barranco, Maria Dolores Chirlaque, [Salamanca-Fernández,E, Rodríguez-Barranco,M, Sánchez,MJ] Andalusian School of Public Health (EASP), Campus Universitario de Cartuja, Granada, Spain. [Salamanca-Fernández,E, Arrebola,JP, Vela,F, Olea,N, Sánchez,MJ] Instituto de Investigación Biosanitaria ibs. GRANADA, Granada, Spain. [Rodríguez-Barranco,M, Amiano,P, Delfrade,J, Chirlaque,MD, Colorado,S, Guevara,M, Sánchez,MJ] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Amiano,P, Jimenez,A] Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, Spain. [Delfrade,J, Guevara,M] Navarra Public Health Institute, Pamplona, Spain. [Delfrade,J, Guevara,M] Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Chirlaque,MD, Colorado,S] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Chirlaque,MD] Department of Health and Sciences, University of Murcia, Murcia, Spain. [Colorado,S] Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia. [Arrebola,JP, Sánchez,MJ] Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain. [Olea,N] Department of Radiology, University of Granada, Granada, Spain. [Agudo,A] Unit of Nutrition and Cancer, Catalan Institute of Oncology - ICO, Nutrition and Cancer Group, Bellvitge Biomedical Research Institute - IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain., and This work was supported by the Ministry of economy and competitiveness and the National Institute of Health: Instituto de Salud Carlos III (ISCIII). Exps: PI14/00067, PI14/01716, PI14/01880, PI14/00556. BA15/00093. FFIS-CC 2016–06 AECC 'Junta provincial de Murcia'. FEDER and AECC 2015. Dr. J.P. Arrebola is under contract within Ramon y Cajal program (RYC-2016-20155, Ministerio de Economía, Industria y Competitividad, Spain). The EPIC-Spain cohort was supported by the Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), the Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain).

Subjects
Oncology, Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Environmental Pollutants [Medical Subject Headings], Male, Neoplasias de la próstata, Health, Toxicology and Mutagenesis, Endocrine Disruptors, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Prostate cancer, Breast cancer, Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Acrylates::Methacrylates::Bisphenol A-Glycidyl Methacrylate [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], education.field_of_study, Factors de risc en les malalties, Hazard ratio, Middle Aged, European Prospective Investigation into Cancer and Nutrition, Health Care::Environment and Public Health::Public Health::Environmental Pollution::Environmental Exposure [Medical Subject Headings], Environmental pollutants, Diseases::Male Urogenital Diseases::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms [Medical Subject Headings], Bisphenol a, Endocrine disruptor, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk [Medical Subject Headings], Neoplasias de la mama, Population study, Female, Public aspects of medicine, RA1-1270, Disruptores endocrinos, Adult, Risk, medicine.medical_specialty, endocrine system, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Risk factors in diseases, Population, Estudios de cohortes, Case-cohort, Check Tags::Male [Medical Subject Headings], Breast Neoplasms, Càncer de mama, Phenols, Bisfenol A glicidil metacrilato, Internal medicine, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Phenols [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], medicine, Humans, Benzhydryl Compounds, education, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Càncer de pròstata, Proportional hazards model, business.industry, urogenital system, Research, Public Health, Environmental and Occupational Health, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Endocrine Disruptors [Medical Subject Headings], Prostatic Neoplasms, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Benzhydryl Compounds [Medical Subject Headings], Environmental Exposure, medicine.disease, Industrial medicine. Industrial hygiene, RC963-969, Check Tags::Female [Medical Subject Headings], Spain, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Sensitivity and Specificity::Limit of Detection [Medical Subject Headings], business, Contaminantes ambientales
Abstract

This work was supported by the Ministry of economy and competitiveness and the National Institute of Health: Instituto de Salud Carlos III (ISCIII). Exps: PI14/00067, PI14/01716, PI14/01880, PI14/00556. BA15/00093. FFIS-CC 2016-06 AECC "Junta provincial de Murcia". FEDER and AECC 2015. Dr. J.P. Arrebola is under contract within Ramon y Cajal program (RYC-2016-20155, Ministerio de Economia, Industria y Competitividad, Spain). The EPIC-Spain cohort was supported by the Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), the Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology -ICO (Spain)., Background Bisphenol A (BPA) is an endocrine disruptor that it is present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident breast and prostate cancer in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC). Methods We designed a case-cohort study within the EPIC-Spain cohort. Study population consisted on 4812 participants from 4 EPIC-Spain centers (547 breast cancer cases, 575 prostate cancer cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Borgan II weighted Cox regression was used to estimate hazard ratios. Results Median follow-up time in our study was 16.9 years. BPA geometric mean serum values of cases and sub-cohort were 1.12 ng/ml vs 1.10 ng/ml respectively for breast cancer and 1.33 ng/ml vs 1.29 ng/ml respectively for prostate cancer. When categorizing BPA into tertiles, a 40% increase in risk of prostate cancer for tertile 1 (p = 0.022), 37% increase for tertile 2 (p = 0.034) and 31% increase for tertile 3 (p = 0.072) was observed with respect to values bellow the limit of detection. No significant association was observed between BPA levels and breast cancer risk. Conclusions We found a similar percentage of detection of BPA among cases and sub-cohort from our population, and no association with breast cancer risk was observed. However, we found a higher risk of prostate cancer for the increase in serum BPA levels. Further investigation is needed to understand the influence of BPA in prostate cancer risk., Ministry of economy and competitiveness, National Institute of Health: Instituto de Salud Carlos III (ISCIII), AECC "Junta provincial de Murcia" PI14/00067- PI14/01716- PI14/01880- PI14/00556- BA15/00093- FFIS-CC 2016-06, Spanish Government RYC-2016-20155, Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, Catalan Institute of Oncology -ICO (Spain)

Published
2021

5. Impact of Rowing Training on Quality of Life and Physical Activity Levels in Female Breast Cancer Survivors

Author

José Carlos Fernández-García, Juan Gavala-González, Amanda Torres-Pérez, [Gavala-González,J] Department of Physical Education and Sports, University of Seville, Seville, Spain. [Gavala-González,J, Torres-Pérez,A, Fernández-García,JC] Researching in Sport Science: Research Group (CTS-563) of the Andalusian Research Plan, Malaga, Spain. [Torres-Pérez,A, Fernández-García,JC] Department of Didactics of Languages, Arts and Sport, University of Malaga, Andalucía-Tech, IBIMA, Malaga, Spain., This research was funded by the 'Researching in Sport Sciences' research group (CTS-563) of the Andalusian Research Plan., and Universidad de Sevilla. Departamento de Educación Física y Deporte

Subjects
Longitudinal study, Calidad de vida, Health, Toxicology and Mutagenesis, Rowing, perceived health, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Quality of life, Cancer Survivors, IPAQ-SF, Supervivientes de cáncer, Medicine, 030212 general & internal medicine, Longitudinal Studies, Stage (cooking), Total Mastectomy, Mastectomy, Water Sports, rowing, exercise, Deportes acuáticos, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Questionnaires [Medical Subject Headings], Middle Aged, Ejercicio físico, Encuestas y cuestionarios, Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Quality of Life [Medical Subject Headings], 030220 oncology & carcinogenesis, Neoplasias de la mama, Female, medicine.medical_specialty, SF-36, Physical activity, Breast Neoplasms, Article, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Mastectomy::Mastectomy, Simple [Medical Subject Headings], 03 medical and health sciences, Breast cancer, breast cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies [Medical Subject Headings], Humans, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys [Medical Subject Headings], business.industry, Breast cancer survivor, Public Health, Environmental and Occupational Health, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], medicine.disease, Check Tags::Female [Medical Subject Headings], quality of life, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity::Exercise [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Mastectomy [Medical Subject Headings], Physical therapy, business
Abstract

The aim of this longitudinal study was to determine whether a rowing training program improved the quality of life and the physical activity levels in female breast cancer survivors (n = 28) (stage 1–4.54%, stage 2–36.36%, stage 3–54.54%, and stage 4–4.54%), diagnosed 4.68 ± 3.00 years previously, who had undergone a subsequent intervention (preservation 56.53% and total mastectomy 43.47%) and had a current mean age of 52.30 ± 3.78 years. The participants (n = 28) engaged in a 12-week training program, each week comprising three sessions and each session lasting 60–90 min. The short form of the International Physical Activity Questionnaire (IPAQ-SF) and the Short Form 36 Health Survey (SF-36) were also administered. The results showed statistically significant improvements in levels of physical activity and in the dimensions of quality of life. We can conclude that a 12-week rowing training program tailored to women who have had breast cancer increases physical activity levels, leading to improved health status and quality of life.

Published
2021

6. Significant Decrease in Annual Cancer Diagnoses in Spain during the COVID-19 Pandemic: A Real-Data Study

Author

Esperanza Torres, Emilio Alba, M. Cobo, Inmaculada Ramos, Ana Godoy, Laura Galvez, Nuria Ribelles, Sofia Ruiz-Medina, Begoña Jimenez, Marta Muñoz-Ayllon, Pablo Rodriguez-Brazzarola, Mireya Cazorla, María José Bermejo, Tamara Diaz-Redondo, Antonio Rueda, Carmen Reyna, Silvia Gil, [Ruiz-Medina,S, Gil,S, Jimenez,B, Diaz-Redondo,T, Cazorla,M, Muñoz-Ayllon,M, Ramos,I, Reyna,C, Bermejo,MJ, Godoy,A, Torres,E, Cobo,M, Galvez,L, Rueda,A, Alba,E, and Ribelles,N] Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga, Spain. [Rodriguez-Brazzarola,P] Grupo de Inteligencia Computacional en Biomedicina, ETSI Ingeniería Informática, Universidad de Málaga, Málaga, Spain.

Subjects
Cancer Research, Pediatrics, medicine.medical_specialty, Diseases::Neoplasms::Neoplasms by Site::Head and Neck Neoplasms [Medical Subject Headings], Coronavirus disease 2019 (COVID-19), Infecciones por coronavirus, COVID-19 pandemic, Article, 03 medical and health sciences, cancer diagnoses, 0302 clinical medicine, Breast cancer, Pandemic, medicine, 030212 general & internal medicine, Medical diagnosis, Pathological, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], RC254-282, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Pandemia, SARS-CoV-2, business.industry, COVID-19, Health Care::Environment and Public Health::Public Health::Disease Outbreaks::Epidemics::Pandemics [Medical Subject Headings], Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], medicine.disease, Neoplasias, Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [Medical Subject Headings], Hospital care, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings], Oncology, 030220 oncology & carcinogenesis, Population study, business, real data
Abstract

The COVID-19 pandemic has caused a profound change in health organizations at both the primary and hospital care levels. This cross-sectional study aims to investigate the impact of the COVID-19 pandemic in the annual rate of new cancer diagnosis in two university-affiliated hospitals. This study includes all the patients with a pathological diagnosis of cancer attended in two hospitals in Málaga (Spain) during the first year of pandemic. This study population was compared with the patients diagnosed during the previous year 2019. To analyze whether the possible differences in the annual rate of diagnoses were due to the pandemic or to other causes, the patients diagnosed during 2018 and 2017 were also compared. There were 2340 new cancer diagnosis compared to 2825 patients in 2019 which represented a decrease of −17.2% (p = 0.0001). Differences in the number of cancer patients diagnosed between 2018 and 2019 (2840 new cases, 0.5% increase) or 2017 and 2019 (2909 new cases, 3% increase) were not statistically significant. The highest number of patients lost from diagnosis in 2020 was in breast cancer (−26.1%), colorectal neoplasms (−16.9%), and head and neck tumors (−19.8%). The study of incidence rates throughout the first year of the COVID-19 pandemic shows that the diagnosis of new cancer patients has been significantly impaired. Health systems must take the necessary measures to restore pre-pandemic diagnostic procedures and to recover lost patients who have not been diagnosed.

Published
2021

7. Role of the Holoenzyme PP1-SPN in the Dephosphorylation of the RB Family of Tumor Suppressors During Cell Cycle

Author

Verdugo-Sivianes, Eva M., Carnero, Amancio, [Verdugo-Sivianes,EM, Carnero,A] Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocio, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Seville, Spain. [Verdugo-Sivianes,EM, Carnero,A] CIBERONC, Instituto de Salud Carlos III, Madrid, Spain., This research was funded by grants from the Ministerio de Ciencia, Innovación y Universidades (MCIU) Plan Estatal de I+D+I 2018, a la Agencia Estatal de Investigación (AEI) y al Fondo Europeo de Desarrollo Regional (MCIU/AEI/FEDER, UE): RTI2018-097455-B-I00, grant from AEI-MICIU/FEDER (RED2018-102723-T), from CIBER de Cáncer (CB16/12/00275), co-funded by FEDER from Regional Development European Funds (European Union), and from Consejeria de Salud (PI-0397-2017) and Consejeria of Economía, Conocimiento, Empresas y Universidad of the Junta de Andalucia (P18-RT-2501). Moreover, a special thanks to the Fundacion AECC and Fundacion Eugenio Rodriguez Pascual for supporting this work.

Subjects
Carcinogénesis, Proteína de retinoblastoma, Dominio catalítico, Células madre, Spinophilin, Anatomy::Cells::Stem Cells::Neoplastic Stem Cells [Medical Subject Headings], Quinasas ciclina-dependientes, Cell cycle, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Tumor Suppressor Proteins::Retinoblastoma Protein [Medical Subject Headings], Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Phosphoric Monoester Hydrolases::Phosphoprotein Phosphatases::Protein Phosphatase 1 [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Breast cancer, PPP1R9B, Proteína fosfatasa 1, Phosphorylation, Phenomena and Processes::Metabolic Phenomena::Metabolism::Phosphorylation [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Cancer, Holoenzimas, Stem cell, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Binding Sites::Catalytic Domain [Medical Subject Headings], Cyclin-dependent kinases, Diseases::Neoplasms::Neoplastic Processes::Carcinogenesis [Medical Subject Headings], Anatomy::Respiratory System::Lung [Medical Subject Headings], Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::Cyclin-Dependent Kinases [Medical Subject Headings], Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Cycle::Interphase::G1 Phase [Medical Subject Headings], Neoplasias, Check Tags::Female [Medical Subject Headings], Retinoblastoma protein, Tumorigenesis, Neoplasias de la mama, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Substrate Specificity [Medical Subject Headings], Catalytic subunit, RB family proteins, Pocket proteins, Holoenzymes, Fosforilación, Phosphatase PP1, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Holoenzymes [Medical Subject Headings]
Abstract

Cell cycle progression is highly regulated by modulating the phosphorylation status of the retinoblastoma protein (pRB) and the other two members of the RB family, p107 and p130. This process is controlled by a balance in the action of kinases, such as the complexes formed by cyclin-dependent kinases (CDKs) and cyclins, and phosphatases, mainly the protein phosphatase 1 (PP1). However, while the phosphorylation of the RB family has been largely studied, its dephosphorylation is less known. Phosphatases are holoenzymes formed by a catalytic subunit and a regulatory protein with substrate specificity. Recently, the PP1-Spinophilin (SPN) holoenzyme has been described as the main phosphatase responsible for the dephosphorylation of RB proteins during the G0/G1 transition and at the end of G1. Moreover, SPN has been described as a tumor suppressor dependent on PP1 in lung and breast tumors, where it promotes tumorigenesis by increasing the cancer stem cell pool. Therefore, a connection between the cell cycle and stem cell biology has also been proposed via SPN/PP1/RB proteins. Yes

Published
2021

8. Evaluation of the Use of Shared Decision Making in Breast Cancer: International Survey

Author

Rubén Trigueros, Luciano Mignini, Manuel Martín-Díaz, Aurora Bueno-Cavanillas, Khalid S. Khan, Marta Maes-Carballo, [Maes-Carballo,M] Unidad de Patología Mamaria del Servicio de Cirugía General, Complexo Universitario Hospitalario de Ourense, Ourense, Spain. [Maes-Carballo,M, Khan,KS, Bueno-Cavanillas,A] Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain. [Martín-Díaz,M] Hospital Básico Santa Ana de Motril, Granada, Spain. [Mignini,L] Unidad de Mastología del Grupo Oroño, Rosario, Argentina. [Khan,KS, and Bueno-Cavanillas,A] CIBER of Epidimiology and Public Health (CIBERESP), Madrid, Spain. [Trigueros,R] Department of Language and Education, University of Antonio de Nebrija, Madrid, Spain. [Bueno-Cavanillas,A] Instituto de Investigación Biosanitaria (IBS), Granada, Spain.

Subjects
Longitudinal study, Health, Toxicology and Mutagenesis, use of shared decision making, lcsh:Medicine, Computer-assisted web interviewing, Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Thinking::Decision Making [Medical Subject Headings], Estudios longitudinales, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Breast cancer, Surveys and Questionnaires, 030212 general & internal medicine, Survey, health care economics and organizations, Shared decision making, Health Care::Health Care Facilities, Manpower, and Services::Health Services::Community Health Services::Consumer Participation::Patient Participation [Medical Subject Headings], longitudinal study, humanities, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings], Encuestas y cuestionarios, 030220 oncology & carcinogenesis, Scale (social sciences), Neoplasias de la mama, Professional association, Psychology, medicine.medical_specialty, education, shared decision making, Decision Making, Breast Neoplasms, Article, Information Science::Information Science::Data Collection::Questionnaires [Medical Subject Headings], 03 medical and health sciences, breast cancer, Patient satisfaction, Toma de decisiones conjunta, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies [Medical Subject Headings], medicine, Humans, survey, Use of shared decision making, Disadvantage, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Toma de decisiones compartidas, lcsh:R, Public Health, Environmental and Occupational Health, International survey, medicine.disease, Cross-Sectional Studies, Family medicine, Patient Participation, Decision Making, Shared
Abstract

Objectives: To assess shared decision-making (SDM) knowledge, attitude and application among health professionals involved in breast cancer (BC) treatment. Materials and Methods: A cross-sectional study based on an online questionnaire, sent by several professional societies to health professionals involved in BC management. There were 26 questions which combined demographic and professional data with some items measured on a Likert-type scale. Results: The participation (459/541, 84.84%) and completion (443/459, 96.51%) rates were high. Participants strongly agreed or agreed in 69.57% (16/23) of their responses. The majority stated that they knew of SDM (mean 4.43 (4.36–4.55)) and were in favour of its implementation (mean 4.58 (4.51–4.64)). They highlighted that SDM practice was not adequate due to lack of resources (3.46 (3.37–3.55)) and agreed on policies that improved its implementation (3.96 (3.88–4.04)). The main advantage of SDM for participants was patient satisfaction (38%), and the main disadvantage was the patients’ paucity of knowledge to understand their disease (24%). The main obstacle indicated was the lack of time and resources (40%). Conclusions: New policies must be designed for adequate training of professionals in integrating SDM in clinical practice, preparing them to use SDM with adequate resources and time provided.

Published
2021

9. Comprehensive genomic profile of heterogeneous long follow-up triple-negative breast cancer and its clinical characteristics shows DNA repair deficiency has better prognostic

Author

Enrique Bargallo-Rocha, Luis I. Terrazas, Clara Díaz-Velásquez, Fernando Vallejo-Lecuona, Fany Iris Porras Reyes, Aldo de la Cruz-Montoya, Javier Oliver, Javier César Mejía-Gómez, Sandra Perdomo, Víctor Pérez-Sánchez, Héctor Martínez Gregorio, Paula Cabrera-Galeana, Cecilia Frecha, Maritza Ramos-Ramírez, Yolanda I. Chirino, Rosalía Quezada-Urban, Felipe Vaca-Paniagua, Luis A. Herrera, Ernesto Rojas-Jiménez, Maybelline Robles-Estrada, Héctor Maldonado-Martinez, [Rojas-Jiménez,E, Díaz-Velásquez,C, Quezada-Urban,R, Martínez Gregorio,H, Vallejo-Lecuona,F, Terrazas,LI, Vaca-Paniagua,F] Laboratorio Nacional en Salud, Diagnóstico Molecular y Efecto Ambiental en Enfermedades Crónico-Degenerativas, Facultad de Estudios Superiores Iztacala, Tlalnepantla, Estado de México, Mexico. [Rojas-Jiménez,E, de la Cruz-Montoya,A, Chirino,YI, Vaca-Paniagua,F] Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, UNAM, Tlalnepantla, Estado de México, Mexico. [Mejía-Gómez,JC] Division of Breast Cancer, Department of Medical Oncology, Mt. Sinai Hospital, University of Toronto, Toronto, ON, Canada. [Quezada-Urban,R] Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. [Quezada-Urban,R] Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. [Porras Reyes,FI, Pérez-Sánchez,VM, Maldonado-Martínez,HA, Bargalló-Rocha,E, Cabrera-Galeana,P, Ramos-Ramírez,M, Alonso Herrera,L, Vaca-Paniagua,F] Instituto Nacional de Cancerología, CDMX, Mexico. [Robles-Estrada,M] Hospital General de Pachuca SSA, Pachuca, Mexico. [Alonso Herrera,L] Instituto Nacional de Medicina Genómica, CDMX, Mexico. [Alonso Herrera,L] Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas-Instituto Nacional de Cancerología, CDMX, Mexico. [Oliver,J] Medical Oncology Service, Hospitales Universitarios Regional y Virgen de la Victoria, Institute of Biomedical Research in Malaga, CIMES, University of Málaga, Málaga, Spain. [Frecha,C] Unidad de Producción Celular del Hospital Regional Universitario de Málaga—IBIMA—Málaga, Málaga, Spain. [Perdomo,S] Instituto de Nutrición, Genética y Metabolismo, Facultad de Medicina, Universidad El Bosque, Bogotá, Colombia. [Perdomo,S] International Agency for Research on Cancer, World Health Organization, Lyon, France., This study was funded by grants from UNAM PAPIIT IN219217 and CONACyT Fondo Sectorial 272573., and Perdomo Lara, Sandra Janneth [0000-0002-4429-3760]

Subjects
0301 basic medicine, Oncology, Terapéutica, Triple Negative Breast Neoplasms, Kaplan-Meier Estimate, whole exome sequencing, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::DNA Repair-Deficiency Disorders [Medical Subject Headings], somatic mutation, Genetics (clinical), Triple-negative breast cancer, Exome sequencing, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], education.field_of_study, biology, treatment, Middle Aged, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [Medical Subject Headings], 030220 oncology & carcinogenesis, Neoplasias de la mama, triple-negative breast cancer, WES, Female, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA [Medical Subject Headings], Adult, medicine.medical_specialty, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], lcsh:QH426-470, DNA repair, Population, Mutational signatures, mutational signatures, Article, 03 medical and health sciences, Breast cancer, Germline mutation, Lymphocytes, Tumor-Infiltrating, Internal medicine, Exome Sequencing, Genetics, medicine, PTEN, Humans, education, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Secuenciación del exoma completo, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis::Kaplan-Meier Estimate [Medical Subject Headings], Somatic mutation, México, Whole exome sequencing, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Neoplasias de la mama triple negativas, medicine.disease, DNA Repair-Deficiency Disorders, Treatment, lcsh:Genetics, 030104 developmental biology, Geographical Locations::Geographic Locations::Americas::North America::Mexico [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Genomic Profile, Mutation, biology.protein, Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocytes, Tumor-Infiltrating [Medical Subject Headings]
Abstract

Triple-negative breast cancer (TNBC) presents a marked diversity at the molecular level, which promotes a clinical heterogeneity that further complicates treatment. We performed a detailed whole exome sequencing profile of 29 Mexican patients with long follow-up TNBC to identify genomic alterations associated with overall survival (OS), disease-free survival (DFS), and pathologic complete response (PCR), with the aim to define their role as molecular predictive factors of treatment response and prognosis. We detected 31 driver genes with pathogenic mutations in TP53 (53%), BRCA1/2 (27%), CDKN1B (9%), PIK3CA (9%), and PTEN (9%), and 16 operative mutational signatures. Moreover, tumors with mutations in BRCA1/2 showed a trend of sensitivity to platinum salts. We found an association between deficiency in DNA repair and surveillance genes and DFS. Across all analyzed tumors we consistently found a heterogeneous molecular complexity in terms of allelic composition and operative mutational processes, which hampered the definition of molecular traits with clinical utility. This work contributes to the elucidation of the global molecular alterations of TNBC by providing accurate genomic data that may help forthcoming studies to improve treatment and survival. This is the first study that integrates genomic alterations with a long follow-up of clinical variables in a Latin American population that is an underrepresented ethnicity in most of the genomic studies.

Published
2020

10. Breast tumor cells promotes the horizontal propagation of EMT, stemness, and metastasis by transferring the MAP17 protein between subsets of neoplastic cells

Author

Amancio Carnero, Sandra Muñoz-Galván, Daniel Otero-Albiol, Elena Pérez-Castejón, José M. García-Heredia, Marco Perez, Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular, Ministerio de Ciencia, Innovación y Universidades (MICINN). España, Agencia Estatal de Investigación. España, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), entro de Investigación Biomédica en Red (CIBER). España, Junta de Andalucía, [García-Heredia,JM, Otero-Albiol,D, Pérez,M, Pérez-Castejón,E, Muñoz-Galván,S, Carnero,A] Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Consejo Superior de Investigaciones Científicas, Seville, Spain. [García-Heredia,JM] Departamento de Bioquímica Vegetal y Biología Molecular, Universidad de Sevilla, Seville, Spain. [García-Heredia,JM, Carnero,A] CIBER de Cancer, Seville, Spain., This work was supported by grants from the Ministerio de Ciencia, Innovación y Universidades (MCIU) Plan Estatal de I+D+I 2018, a la Agencia Estatal de Investigación (AEI) y al Fondo Europeo de Desarrollo Regional (MCIU/AEI/FEDER, UE): RTI2018–097455-B-I00, from AEIMICIU/FEDER (RED2018–102723-T), from CIBER de Cáncer (CB16/12/00275), co-funded by FEDER from Regional Development European Funds (European Union), from Consejería de Salud (PI-0397–2017) and Consejería of Economía, Conocimiento, Empresas y Universidad de Junta de Andalucía (P18-RT-2501)., Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Red Temática de Investigación Cooperativa en Cáncer (España), Fundación Científica Asociación Española Contra el Cáncer, and Fundación Eugenio Rodríguez Pascual

Subjects
0301 basic medicine, Cancer Research, Cell, Exosomes, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression [Medical Subject Headings], Metastasis, Exosomas, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Breast cancer, 0302 clinical medicine, MicroARNs, Cancer stem cells, Desmetilación, Extracellular matrix, Diseases::Neoplasms [Medical Subject Headings], lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Neoplasias, MAP17, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Neoplasias de la mama, Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Cytoplasmic Vesicles::Transport Vesicles::Exosomes [Medical Subject Headings], Notch signaling pathway, Biology, lcsh:RC254-282, Article, 03 medical and health sciences, Downregulation and upregulation, Diseases::Neoplasms::Neoplastic Processes::Neoplasm Metastasis [Medical Subject Headings], microRNA, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma [Medical Subject Headings], medicine, Epithelial–mesenchymal transition, Molecular Biology, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Inflammation, Inflamación, Carcinoma, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic [Medical Subject Headings], medicine.disease, Microvesicles, Demethylation, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [Medical Subject Headings], MicroRNAs, 030104 developmental biology, Tumor progression, Cancer research, Neoplasm, Gene expression, Breast neoplasms, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings], Expresión génica
Abstract

MAP17 (PDZK1IP1) is a small protein regulating inflammation and tumor progression, upregulated in a broad range of carcinomas. MAP17 levels increase during tumor progression in a large percentage of advanced tumors. In the present work, we explored the role of this protein shaping tumor evolution. Here we show that in breast cancer, cells increased MAP17 levels in tumors by demethylation induced multiple changes in gene expression through specific miRNAs downregulation. These miRNA changes are dependent on Notch pathway activation. As a consequence, epithelial mesenchymal transition (EMT) and stemness are induced promoting the metastatic potential of these cells both in vitro and in vivo. Furthermore, MAP17 increased the exosomes in tumor cells, where MAP17 was released as cargo, and this horizontal propagation also increased the EMT in the recipient cells. Importantly, an antibody against MAP17 in the media reduces the EMT and stemness alterations promoted by the conditioned media from MAP17-expressing cells. Therefore, MAP17 expression promotes the horizontal propagation of EMT and metastasis by transferring the MAP17 protein between subsets of neoplastic cells. Thus, MAP17 can be used to describe a new mechanism for cell malignity at distance, without the involvement of genetic or epigenetic modifications. MAP17 can also be taken in consideration as new target for metastatic high-grade breast tumors., This work was supported by grants from the Ministerio de Ciencia, Innovación y Universidades (MCIU) Plan Estatal de I+D+I 2018, a la Agencia Estatal de Investigación (AEI) y al Fondo Europeo de Desarrollo Regional (MCIU/AEI/FEDER, UE): RTI2018–097455-B-I00; from AEIMICIU/FEDER (RED2018–102723-T); from CIBER de Cáncer (CB16/12/00275), co-funded by FEDER from Regional Development European Funds (European Union); from Consejería de Salud (PI-0397–2017) and Consejería of Economía, Conocimiento, Empresas y Universidad de Junta de Andalucía (P18-RT-2501). Also especial thanks to the Fundación AECC and Fundación Eugenio Rodriguez Pascual for supporting this work.

Published
2020

11. Breast and Gut Microbiota Action Mechanisms in Breast Cancer Pathogenesis and Treatment

Author

Laborda-Illanes, Aurora, Sanchez-Alcoholado, Lidia, Dominguez-Recio, María Emilia, Jimenez-Rodriguez, Begoña, Lavado, Rocío, Comino-Méndez, Iñaki, Alba, Emilio, Queipo-Ortuño, María Isabel, [Laborda-Illanes,A, Sanchez-Alcoholado,L, Dominguez-Recio,ME, Jimenez-Rodriguez,B, Lavado,R, Comino-Méndez,I, Alba,E, Queipo-Ortuño,MI] Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, Málaga, Spain. [Laborda-Illanes,A, Sanchez-Alcoholado,L] Facultad de Medicina, Universidad de Málaga, Málaga, Spain., and This work was supported in part by PE-0106-2019 from the Consejería de Salud de la Junta de Andalucía, C19047-2018 from Fundación Unicaja and UMA18-FEDERJA-042 from UMA-FEDER. Maria Isabel Queipo-Ortuño is recipient of a 'Miguel Servet Type II' program (CPI13/00003) from ISCIII, co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Madrid, Spain and also belongs to the regional 'Nicolas Monardes' research program of the Consejería de Salud (C-0030-2018, Junta de Andalucía, Spain. Aurora Laborda-Illanes was recipient of a predoctoral grant PFIS-ISCIII (FI19-00112) co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Madrid, Spain. Lidia Sanchez-Alcoholado was recipient of a predoctoral grant (PE-0106-2019) from the Consejería de Salud y Familia (co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Andalucia, Spain).

Subjects
Prebióticos, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Breast cancer, Inmunidad, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Sexual Development::Climacteric::Menopause::Postmenopause [Medical Subject Headings], Estrobolome, Immune responds, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Inflammation, Inflamación, Microbiota, Probiotics, Anticancer therapy, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [Medical Subject Headings], Probióticos, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic [Medical Subject Headings], Phenomena and Processes::Immune System Phenomena::Immunity [Medical Subject Headings], Antineoplásicos, Prebiotics, Phenomena and Processes::Microbiological Phenomena::Microbiota [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Neoplasias de la mama, Technology and Food and Beverages::Food and Beverages::Food::Dietary Supplements [Medical Subject Headings], Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Dysbiosis [Medical Subject Headings], Epigenetic modulation, Chemicals and Drugs::Carbohydrates::Polysaccharides::Polysaccharides, Bacterial::Prebiotics [Medical Subject Headings], Epigénesis genética, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings]
Abstract

In breast cancer (BC) the employment of sequencing technologies for metagenomic analyses has allowed not only the description of the overall metagenomic landscape but also the specific microbial changes and their functional implications. Most of the available data suggest that BC is related to bacterial dysbiosis in both the gut microenvironment and breast tissue. It is hypothesized that changes in the composition and functions of several breast and gut bacterial taxa may contribute to BC development and progression through several pathways. One of the most prominent roles of gut microbiota is the regulation of steroid-hormone metabolism, such as estrogens, a component playing an important role as risk factor in BC development, especially in postmenopausal women. On the other hand, breast and gut resident microbiota are the link in the reciprocal interactions between cancer cells and their local environment, since microbiota are capable of modulating mucosal and systemic immune responses. Several in vivo and in vitro studies show remarkable evidence that diet, probiotics and prebiotics could exert important anticarcinogenic effects in BC. Moreover, gut microbiota have an important role in the metabolism of chemotherapeutic drugs and in the activity of immunogenic chemotherapies since they are a potential dominant mediator in the response to cancer therapy. Then, the microbiome impact in BC is multi-factorial, and the gut and breast tissue bacteria population could be important in regulating the local immune system, in tumor formation and progression and in therapy response and/or resistance. Yes

Published
2020

12. Quality and reporting of clinical guidelines for breast cancer treatment: A systematic review

Author

Maes-Carballo, Marta, Mignini, Luciano, Martín-Díaz, Manuel, Bueno-Cavanillas, Aurora, Khan, Khalid Saeed, [Maes-Carballo,M] Department of General Surgery, Complexo Hospitalario de Ourense, Ourense, Spain. [Maes-Carballo,M, Bueno-Cavanillas,A, Khan,KS] Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain. [Mignini,L] Unidad de Mastología de Grupo Oro~no, Rosario, Argentina. [Martín-Díaz,M] Department of General Surgery, Hospital de Motril, Granada, Spain. [Bueno-Cavanillas,A, and Khan,KS] CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Bueno-Cavanillas,A] Instituto de Investigación Biosanitaria IBS, Granada, Spain.

Subjects
RIGHT, Consensus, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Group Processes::Consensus [Medical Subject Headings], Terapéutica, Revisión sistemática, Guidelines, AGREE II, Health Care::Health Services Administration::Quality of Health Care::Quality Assurance, Health Care::Guidelines as Topic::Practice Guidelines as Topic [Medical Subject Headings], Treatment, Guía de práctica clínica, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Breast cancer, Information Science::Information Science::Medical Informatics::Medical Informatics Applications::Information Systems::Databases as Topic::Databases, Bibliographic [Medical Subject Headings], Consenso, Check Tags::Female [Medical Subject Headings], Neoplasias de la mama, Appraisal instruments, Guías como asunto, Quality of guidelines, Clinical practice guidelines, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings]
Abstract

Background: High-quality, well-reported clinical practice guidelines (CPGs) and consensus statements (CSs) underpinned by systematic reviews are needed. We appraised the quality and reporting of CPGs and CSs for breast cancer (BC) treatment. Methods: Following protocol registration (Prospero no: CRD42020164801), CPGs and CSs on BC treatment were identified, without language restrictions, through a systematic search of bibliographic databases (MEDLINE, EMBASE, Web of Science, Scopus, CDSR) and online sources (12 guideline databases and 51 professional society websites) from January 2017 to June 2020. Data were extracted in duplicate assessing overall quality using AGREE II (% of maximum score) and reporting compliance using RIGHT (% of total 35 items); reviewer agreement was 98% and 96% respectively. Results: There were 59 relevant guidance documents (43 CPGs, 16 CSs), of which 20 used systematic reviews for evidence synthesis. The median overall quality was 54.0% (IQR 35.9-74.3) and the median overall reporting compliance was 60.9% (IQR 44.5-84.4). The correlation between quality and reporting was 0.9. Compared to CSs, CPGs had better quality (55.4% vs 44.2%; p = 0.032) and reporting (67.18% vs 44.5%; p = 0.005). Compared to subjective methods of evidence analysis, guidance documents that used systematic reviews had better quality (76.3% vs 51.4%; p = 0.001) and reporting (87.1% vs 59.4%; p = 0.001). Conclusion: The quality and reporting of CPGs and CSs in BC treatment were moderately strong. Systematic reviews should be used to improve the quality and reporting of CPGs and CSs. Yes

Published
2020

13. Resistance to Neoadjuvant Treatment in Breast Cancer: Clinicopathological and Molecular Predictors

Author

Chica-Parrado, María Rosario, Godoy-Ortiz, Ana, Jiménez, Begoña, Ribelles, Nuria, Barragan, Isabel, Alba, Emilio, [Chica-Parrado,MR, Godoy-Ortiz,A, Jiménez,B, Ribelles,N, Barragan,I, Alba,E] Institute of Biomedical Research in Malaga (IBIMA), Regional and Virgen de la Victoria University Hospitals, Málaga, Spain. [Chica-Parrado,MR, Alba,E] Cancer Molecular Biology Group, Medical Research Center, University of Málaga (UMA), Málaga, Spain. [Godoy-Ortiz,A, Alba,E] Medical Oncology Service Intercentros, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga, Spain. [Barragan,I] Group of Pharmacoepigenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., and This research was funded by the Instituto de Salud Carlos III Grant PI15/01823 (to Emilio Alba, María Rosario Chica-Parrado, and Begoña Jiménez), the European Commission MSCA Grant 799,818 (to Isabel Barragán.), and the Grant for Research Support of Clinical Units of the Andalusian Health System SA0263/2017 (to Isabel Barragán). The APC was funded by the Institute of Biomedical Research in Malaga Instituto de investigación Biomédica de Málaga (IBIMA).

Subjects
Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Recurrence [Medical Subject Headings], Pathological complete response, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], Residual disease, Trastuzumab, Predictive markers, Neoadjuvant chemotherapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Breast cancer, Terapia neoadyuvante, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Neoplasias de la mama, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Anthropometry::Body Weights and Measures::Tumor Burden [Medical Subject Headings], Diseases::Neoplasms::Neoplastic Processes::Neoplasm Metastasis::Neoplasm Micrometastasis [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], Chemicals and Drugs::Biological Factors::Biological Markers::Tumor Markers, Biological::Receptor, erbB-2 [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings]
Abstract

Neoadjuvant Chemotherapy (NAC) in Breast Cancer (BC) has proved useful for the reduction in tumor burden prior to surgery, allowing for a more extensive breast preservation and the eradication of subjacent micrometastases. However, the impact on prognosis is highly dependent on the establishment of Pathological Complete Response (pCR), in particular for Triple Negative (TN) and Hormonal Receptor negative/Human Epidermal growth factor Receptor 2 positive (HR-/HER2+) subtypes. Several pCR predictors, such as PAM50, Integrative Cluster (IntClust), mutations in PI3KCA, or the Trastuzumab Risk model (TRAR), are useful molecular tools for estimating response to treatment and are prognostic. Major evolution events during BC NAC that feature the Residual Disease (RD) are the loss of HR and HER2, which are prognostic of bad outcome, and stemness and immune depletion-related gene expression aberrations. This dynamic nature of the determinants of response to BC NAC, together with the extensive heterogeneity of BC, raises the need to discern the individual and subtype-specific determinants of resistance. Moreover, refining the current approaches for a comprehensive monitoring of tumor evolution during treatment, RD, and eventual recurrences is essential for identifying new actionable alterations and the integral best management of the disease. Yes

Published
2020

14. Rowing Training in Breast Cancer Survivors: A Longitudinal Study of Physical Fitness

Author

José Carlos Fernández-García, Juan Gavala-González, Pere Mercadé-Melé, Ismael Gálvez-Fernández, Universidad de Sevilla. Departamento de Educación Física y Deporte, Junta de Andalucía. Plan de Investigación, [Gavala-González,J] Department of Physical Education and Sports, University of Seville, Seville, Spain. [Gálvez-Fernández,I, Fernández-García,JC] Department of Didactics of Languages, Arts and Sport, University of Malaga, Andalucia-Tech, IBIMA, Malaga, Spain. [Mercadé-Melé,P] Department of Statistics and Econometrics, University of Malaga, Andalucia-Tech, Malaga, Spain., and This research was funded by the 'Researching in Sport Sciences' research group (CTS-563) of the Andalusian Research Plan.

Subjects
Longitudinal study, Health, Toxicology and Mutagenesis, Rowing, Physical fitness, lcsh:Medicine, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Quality of life, heart rate, 030212 general & internal medicine, Longitudinal Studies, Survivors, Mastectomy, Water Sports, education.field_of_study, anthropometry, rowing, Hand Strength, Middle Aged, fitness, Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Quality of Life [Medical Subject Headings], 030220 oncology & carcinogenesis, Neoplasias de la mama, Female, Persons::Persons::Survivors [Medical Subject Headings], medicine.medical_specialty, Population, Breast Neoplasms, Article, 03 medical and health sciences, breast cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies [Medical Subject Headings], Heart rate, Deportes Acuáticos, medicine, Humans, education, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Muscle Strength::Hand Strength [Medical Subject Headings], business.industry, Health Care::Population Characteristics::Health::Physical Fitness [Medical Subject Headings], lcsh:R, Public Health, Environmental and Occupational Health, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Anthropometry, Antropometría, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Mastectomy [Medical Subject Headings], Physical Fitness, Physical therapy, Lean body mass, Quality of Life, business, human activities
Abstract

The aim of this study was to determine whether a rowing training program leads to improvements in physical fitness and body composition in women who have survived breast cancer (53.70 &plusmn, 7.88 years). The participants (n = 30) completed a twelve-week training program consisting of three sessions per week, with each session lasting from sixty to ninety minutes. An anthropometric and general physical fitness assessment was performed before and after the program. The results showed statistically significant improvements in all the physical fitness tests performed: sit and reach (2.82 cm), back scratch, dominant (3.29 cm), back scratch, non-dominant (4.59 cm), counter movement jump (1.91 cm), hand grip, dominant (2.54 kgf), hand grip, non-dominant (2.53 kgf), chair stand (2.56 rep), and six-minute walk (51.56 m). In addition, a significant improvement was observed in the efficiency of the cardiovascular system measured by heart rate, in beats per minute (bpm), both before (&minus, 12.63 bpm) and after the six-minute walk test (&minus, 11.46 bpm). The evaluated body composition parameters also improved, specifically total lean mass (2.18 kg) and the percentage of total body fat (&minus, 2.63%). We can therefore conclude that rowing training programs can be a strategy to be considered for improving physical fitness in this population given the improvement obtained in both anthropometric and physical fitness variables, thus leading to better health and quality of life.

Published
2020

15. ZNF577 Methylation Levels in Leukocytes From Women With Breast Cancer Is Modulated by Adiposity, Menopausal State, and the Mediterranean Diet

Author

Paula M. Lorenzo, Andrea G. Izquierdo, Angel Diaz-Lagares, Marcos C. Carreira, Manuel Macias-Gonzalez, Juan Sandoval, Juan Cueva, Rafael Lopez-Lopez, Felipe F. Casanueva, Ana B. Crujeiras, [Lorenzo,PM, Izquierdo,AG, Crujeiras,AB] Laboratory of Epigenomics in Endocrinology and Nutrition (EpiEndoNut), Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), Santiago de Compostela, Spain. [Izquierdo,AG, Carreira,MC, Macias-Gonzalez,M, Casanueva,FF, Crujeiras,AB] CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEOBN), Instituto de Salud Carlos III, Madrid, Spain. [Diaz-Lagares,A] Cancer Epigenetics, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain. [Diaz-Lagares,A, Lopez-Lopez,R] CIBER de Oncologia (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. [Carreira,MC, Casanueva,FF] Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain. [Macias-Gonzalez,M] Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA) and CIBEROBN, Málaga, Spain. [Sandoval,J] Biomarkers and Precision Medicine Unit and Epigenomics Core Facility, Health Research Institute La Fe, Valencia, Spain. [Cueva,J, Lopez-Lopez,R] Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain., and This study was supported by the Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y Nutricion.

Subjects
0301 basic medicine, Epigenomics, obesity, Ciencias de la nutrición, Mediterranean diet, Endocrinology, Diabetes and Metabolism, Células sanguíneas, Obesidad, Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Physiology, Overweight, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Fat Distribution::Adiposity [Medical Subject Headings], Diet, Mediterranean, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Body Mass Index, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Endocrinology, Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Methylation [Medical Subject Headings], Anatomy::Cells::Blood Cells::Leukocytes [Medical Subject Headings], Leukocytes, Promoter Regions, Genetic, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Size::Body Weight::Overweight::Obesity [Medical Subject Headings], Original Research, Adiposity, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Base Sequence::GC Rich Sequence::CpG Islands [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Nutrition Therapy::Diet Therapy::Diet, Mediterranean [Medical Subject Headings], Methylation, Middle Aged, Prognosis, Neoplasias, DNA-Binding Proteins, nutrition, Metilación, Neoplasias de la mama, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins [Medical Subject Headings], Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Climacteric::Menopause [Medical Subject Headings], Female, medicine.symptom, Menopause, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Base Sequence::Regulatory Sequences, Nucleic Acid::Promoter Regions, Genetic [Medical Subject Headings], Adult, 030209 endocrinology & metabolism, Breast Neoplasms, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors [Medical Subject Headings], Phenomena and Processes::Chemical Phenomena::Chemical Processes::Organic Chemistry Processes::Alkylation::Methylation [Medical Subject Headings], 03 medical and health sciences, Breast cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], medicine, Biomarkers, Tumor, cancer, Humans, Epigenetics, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Computational Biology::Genomics::Epigenomics [Medical Subject Headings], Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], lcsh:RC648-665, epigenetics, business.industry, Cancer, biomarkers, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], DNA Methylation, medicine.disease, Obesity, 030104 developmental biology, Biomarcadores, Check Tags::Female [Medical Subject Headings], Spain, Epigenómica, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], CpG Islands, blood cells, business, Body mass index, Follow-Up Studies, Transcription Factors
Abstract

The methylation levels of ZNF577 in breast tumors has been previously identified as a possible epigenetic mark of breast cancer associated with obesity. The aim of the current study was to investigate differences in methylation levels of ZNF577 depending on obesity, menopausal state and dietary pattern in blood leukocytes, a non-invasive sample. The methylation levels of ZNF577 of two CpG sites (CpGs) located in promoter and island previously identified as differentially methylated according to adiposity and menopausal state by 450 k array (cg10635122, cg03562414) were evaluated by pyrosequencing in DNA from the blood leukocytes of breast cancer patients [n = 90; n = 64 (71.1%) overweight/obesity and n = 26 (28.9%) normal-weight] and paired tumor tissue biopsies (n = 8 breast cancer patients with obesity; n = 3/5 premenopausal/postmenopausal women). Differences in methylation levels were evaluated at each CpGs individually and at the mean of the two evaluated CpGs. Adherence to the Mediterranean diet was evaluated using the MEDAS-validated questionnaire, and the consumption of food groups of interest was also evaluated using the recommended intakes of the Sociedad Española de Nutricion Comunitaria. The methylation levels of ZNF577 were correlated between paired leukocytes and breast tumor biopsies (r = 0.62; p = 0.001). Moreover, higher methylation was found in leukocytes from patients with obesity (p = 0.002) and postmenopausal patients (p = 0.022) than patients with normal-weight or premenopausal, respectively. After adjusting for the body mass index and age, higher levels of ZNF577 methylation were also found in women with greater adherence to the Mediterranean diet (p = 0.017) or specific foods. Relevantly, the methylation levels of ZNF577 showed a good ability for fish consumption detection [area under the ROC curve (AUC) = 0.72; p = 0.016]. In conclusion, the association between methylation of ZNF577 and adiposity, menopausal state, and adherence to the Mediterranean diet can be detected in the blood leukocytes. The results guarantee the need of performing further studies in longer longitudinal cohorts in order to elucidate the role of ZNF577 methylation in the association between breast cancer, adiposity and dietary patterns. Yes

Published
2020

16. Physical activity and risks of breast and colorectal cancer : a Mendelian randomisation analysis

Author

Michael O. Woods, Fränzel J.B. van Duijnhoven, Tilman Kühn, Graham G. Giles, Temitope O. Keku, Konstantinos K. Tsilidis, Andrew T. Chan, Mingyang Song, Michael Hoffmeister, Gad Rennert, Tabitha A. Harrison, Anna H. Wu, Kenneth Offit, Mark A. Jenkins, Elizabeth A Platz, Sabina Sieri, Noralane M Lindor, John D. Potter, D Timothy Bishop, Barbara L. Banbury, Anne M. May, Sonja I. Berndt, José María Huerta, Antonia Trichopoulou, Paul D.P. Pharoah, Niki Dimou, Christopher I. Li, Roger L. Milne, Marc J. Gunter, Hermann Brenner, Martha L. Slattery, Catherine M. Tangen, Gianluca Severi, Richard M. Martin, Nabila Kazmi, Ruth C. Travis, Sanford D. Markowitz, Jeroen R. Huyghe, Heather Hampel, Ulrike Peters, John L. Hopper, Brigid M. Lynch, Krasimira Aleksandrova, Alicja Wolk, Merete Ellingjord-Dale, Li Li, Bethany Van Guelpen, Sergi Castellví-Bel, Edward Giovannucci, Steven J Gallinger, Annika Lindblom, Cornelia M. Ulrich, Stephen B. Gruber, Stephanie L. Schmit, Jenny Chang-Claude, Lorena Moreno, Victor Moreno, Nikos Papadimitriou, Stephen N. Thibodeau, Elio Riboli, Sophia Harlid, Polly A. Newcomb, Pavel Vodicka, Demetrius Albanes, Bas Bueno-de-Mesquita, Maria J. Sánchez, Sarah J Lewis, Timothy Robinson, Daniel D Buchanan, Loic Le Marchand, Carlo La Vecchia, Robert E Schoen, Neil Murphy, Giovanna Masala, Evelyn M. Monninkhof, Jane C. Figueiredo, Andrea Gsur, Jochen Hampe, Vittorio Perduca, Li Hsu, Emily White, Peter T. Campbell, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, University of Bristol [Bristol], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Epidemiology, German Institute of Human Nutrition, Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), The Cancer, Ageing and Somatic Mutation Programme [Cambridgeshire, UK], The Wellcome Trust Sanger Institute [Cambridge], Division of Cancer Epidemiology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Harvard School of Public Health, Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Medical Department 1 [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Ohio State University [Columbus] (OSU), FESTO, Universität Stuttgart [Stuttgart], Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Medical Genetics, HMNC Brain Health, Department of Clinical Sciences and Community Health [Milan, Italy], Università degli Studi di Milano [Milano] (UNIMI), University of Hawai‘i [Mānoa] (UHM), Chinese Center for Disease Control and Prevention, Department of Clinical Genetics, Karolinska University Hospital [Stockholm], Mayo Clinic, Case Western Reserve University [Cleveland], Cancer Risk Factors and LifeStyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Cancer Epidemiology Centre, Cancer Council Victoria, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Memorial Sloane Kettering Cancer Center [New York], Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Department of Oncology, University of Cambridge [UK] (CAM), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, School of Public Health [London, UK] (Faculty of Medicine), Andalusian School of Public Health [Granada], Istituto Nazionale dei Tumori, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Mayo Clinic [Rochester], University of Oxford [Oxford], WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], Helmholtz Centre for Ocean Research [Kiel] (GEOMAR), Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Karolinska Institutet [Stockholm], Nutrition and Metabolism Section, International Agency for Research on Cancer, [Papadimitriou,N, Dimou,N, Gunter,MJ, Murphy,N] Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Tsilidis,KK, Ellingjord-Dale,M, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Banbury,B, Harrison,TA, Hsu,L, Huyghe,JR, Li,CI, Newcomb,PA, Potter,JD, White,E, Peters,U] Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Martin,RM, Kazmi,N] MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. [Martin,RM, Lewis,SJ, Robinson,TM] Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK. [Martin,RM] National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK. [Albanes,D, Berndt,SI] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MA, USA. [Aleksandrova,K] German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Bishop,DT] Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK. [Brenner,H, Hoffmeister,M] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Brenner,H] Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. [Brenner,H] German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. [Buchanan,DD, Giles,GG, Hopper,JL, Jenkins,MA, Lynch,B, Milne,R] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. [Buchanan,DD] Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. [Buchanan,DD] Genetic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, VIC, Australia [Bueno-de-Mesquita,B] Former senior scientist, Dept. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), BA Bilthoven, Netherlands. [Bueno-de-Mesquita,B] Former associate professor, Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands. [Bueno-de-Mesquita,B] ormer visiting professor, Dept. of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, St Mary’s Campus, Norfolk Place, London, London, UK. [Bueno-de-Mesquita,B] Former academic Icon / visiting professor, Dept. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Pantai Valley, Kuala Lumpur, Malaysia. [Campbell,PT] Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA. [Castellví-Bel,S, Moreno,L] Gastroenterology Department, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain. [Chan,AT, Song,M] Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Chan,AT, Song,M] Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Chang-Claude,J, Kühn,T] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Chang-Claude,J] University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany. [Figueiredo,JC] Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. [Figueiredo,JC] Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Gallinger,SJ] Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. [Giles,GG, Milne,R] Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia. [Giovannucci,E, Song,M] Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. [Giovannucci,E, Song,M] Department of Nutrition, T.H. H, Chan School of Public Health, Boston, MA, USA. [Giovannucci,E] Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. [Gruber,SB, Schmit,SL] Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Gsur,A] Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria. [Hampe,J] Department of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany. [Hampel,H] Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. [Harlid,S] Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden. [Hopper,JL] Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea. [Hsu,L] Department of Biostatistics, University of Washington, Seattle, WA, USA. [Huerta,JM, Moreno,V, Sánchez,MJ] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Keku,TO] Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA. [La Vecchia,C, Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. [La Vecchia,C] Dept. of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano, Italy. [Le Marchand,L] University of Hawaii Cancer Center, Honolulu, HI, USA. [Li,L] Department of Family Medicine, University of Virginia, Charlottesville, VA, USA. [Lindblom,A] Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. [Lindblom,A] Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. [Lindor,NM] Department of Health Science Research, Mayo Clinic, Scottsdale, AZ, USA. [Lynch,B] Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. [Markowitz,SD] Departments of Medicine and Genetics, Case Comprehensive Cancer Center, Case Western Reserve University, and University Hospitals of Cleveland, Cleveland, OH, USA. [Masala,G] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. [May,AM, Monninkhof,E] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, GA UTRECHT, Netherlands. [Milne,R] Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. [Moreno,V] Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Moreno,V] Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain. [Newcomb,PA] School of Public Health, University of Washington, Seattle, WA, USA. [Offit,K] Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. [Offit,K] Department of Medicine, Weill Cornell Medical College, New York, NY, USA. [Perduca,V, Severi,G] CESP, Fac. de médecine - Univ. ParisSud, Fac. de médecine - UVSQ I, Université Paris-Saclay, Villejuif, France. [Perduca,V, Severi,G] Gustave Roussy, Villejuif, France. [Perduca,V] Laboratoire de Mathématiques Appliquées MAP5 (UMR CNRS 8145), Université Paris Descartes, Paris, France. [Pharoah,PDP] Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Platz,EA] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. [Rennert,G] Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel. [Rennert,G] 7Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. [Rennert,G] Clalit National Cancer Control Center, Haifa, Israel. [Sánchez,MJ] Andalusian School of Public Health, Biomedical Research Institute ibs.GRANADA, University of Granada, Granada, Spain. [Schmit,SL] Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. [Schoen,RE] Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. [Sieri,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Slattery,ML] Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. [Tangen,CM] SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Thibodeau,SN] Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Ulrich,CM] Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA. [van Duijnhoven,FJB] Division of Human Nutrition, Wageningen University and Research, Wageningen, Netherlands. [Van Guelpen,B] Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden. [Van Guelpen,B] Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden. [Vodicka,P] Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic. [Vodicka,P] Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic. [Vodicka,P] Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic. [White,E, Peters,U] Department of Epidemiology, University of Washington, Seattle, WA, USA. [Wolk,A] Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. [Woods,MO] Memorial University of Newfoundland, Discipline of Genetics, St. John’s, Canada. [Wu,AH] University of Southern California, Preventative Medicine, Los Angeles, CA, USA., This work was supported by the National Cancer Institute, the International Agency for Research on Cancer and a Cancer Research UK program grant (C18281/A19169 to RMM, SJL & NK). RMM was supported by the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funding sources for BCAC, CCFR, GECCO, and CORECT consortia are presented in detail in the appendix in the Supplementary material., Tsilidis, Konstantinos K [0000-0002-8452-8472], Martin, Richard M [0000-0002-7992-7719], Lewis, Sarah J [0000-0003-4311-6890], Robinson, Timothy M [0000-0003-0933-646X], Timothy Bishop, D [0000-0002-8752-8785], Buchanan, Daniel D [0000-0003-2225-6675], Chan, Andrew T [0000-0001-7284-6767], Giles, Graham G [0000-0003-4946-9099], Gsur, Andrea [0000-0002-9795-1528], Hampe, Jochen [0000-0002-2421-6127], Hampel, Heather [0000-0001-7558-9794], Harlid, Sophia [0000-0001-8540-6891], Harrison, Tabitha A [0000-0002-4173-7530], María Huerta, José [0000-0002-9637-3869], Huyghe, Jeroen R [0000-0001-6027-9806], Jenkins, Mark A [0000-0002-8964-6160], La Vecchia, Carlo [0000-0003-1441-897X], Masala, Giovanna [0000-0002-5758-9069], Milne, Roger [0000-0001-5764-7268], Moreno, Victor [0000-0002-2818-5487], Newcomb, Polly A [0000-0001-8786-0043], Perduca, Vittorio [0000-0003-0339-0473], Pharoah, Paul D P [0000-0001-8494-732X], Potter, John D [0000-0001-5439-1500], Rennert, Gad [0000-0002-8512-068X], Riboli, Elio [0000-0001-6795-6080], Schmit, Stephanie L [0000-0001-5931-1194], Schoen, Robert E [0000-0001-7153-2766], Van Guelpen, Bethany [0000-0002-9692-101X], Wolk, Alicja [0000-0001-7387-6845], Peters, Ulrike [0000-0001-5666-9318], Murphy, Neil [0000-0003-3347-8249], Apollo - University of Cambridge Repository, Tsilidis, Konstantinos K. [0000-0002-8452-8472], Martin, Richard M. [0000-0002-7992-7719], Lewis, Sarah J. [0000-0003-4311-6890], Timothy Bishop, D. [0000-0002-8752-8785], Buchanan, Daniel D. [0000-0003-2225-6675], Chan, Andrew T. [0000-0001-7284-6767], Giles, Graham G. [0000-0003-4946-9099], Harrison, Tabitha A. [0000-0002-4173-7530], Huyghe, Jeroen R. [0000-0001-6027-9806], Jenkins, Mark A. [0000-0002-8964-6160], Newcomb, Polly A. [0000-0001-8786-0043], Pharoah, Paul D. P. [0000-0001-8494-732X], Potter, John D. [0000-0001-5439-1500], Schmit, Stephanie L. [0000-0001-5931-1194], Schoen, Robert E. [0000-0001-7153-2766], and Pharoah, Paul DP [0000-0001-8494-732X]

Subjects
Oncology, Epidemiology, Colorectal cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Accelerometry [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Molecular Epidemiology::Mendelian Randomization Analysis [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Breast cancer, Epidemiology of cancer, Accelerometry, Odds Ratio, lcsh:Science, skin and connective tissue diseases, Cancer genetics, ComputingMilieux_MISCELLANEOUS, Cancer, 0303 health sciences, Biobank, 3. Good health, 030220 oncology & carcinogenesis, ICEP, Factores de riesgo, medicine.medical_specialty, Science, 631/67/2324, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Colorectal Neoplasms, Hereditary Nonpolyposis [Medical Subject Headings], Breast Neoplasms/genetics, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Càncer colorectal, Anthropology, Education, Sociology and Social Phenomena::Human Activities::Exercise [Medical Subject Headings], Humans, Epidemiologia, Exercise, VLAG, Cancer och onkologi, 45, 631/67/1347, Odds ratio, Mendelian Randomization Analysis, medicine.disease, Colorectal Neoplasms/genetics, 030104 developmental biology, Analyses, Risk factors, Check Tags::Female [Medical Subject Headings], Cancer and Oncology, lcsh:Q, Breast neoplasms, 0301 basic medicine, 631/67/1504/1885, Nutrition and Disease, General Physics and Astronomy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Risk Factors, Neoplasias colorrectales, Voeding en Ziekte, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds Ratio [Medical Subject Headings], Multidisciplinary, article, Public Health, Global Health, Social Medicine and Epidemiology, Polymorphism, Single Nucleotide/genetics, Ejercicio físico, Neoplasias de la mama, Female, Colorectal Neoplasms, 631/67, 141, Breast Neoplasms, 45/23, Polymorphism, Single Nucleotide, Colorectal neoplasms, Càncer de mama, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings], Cancer epidemiology, 631/67/68, Internal medicine, Mendelian randomization, medicine, Journal Article, Life Science, Genetic Predisposition to Disease, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], 030304 developmental biology, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], business.industry, General Chemistry, Physical fitness, Confidence interval, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Condició física
Abstract

Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers., United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI), International Agency for Research on Cancer, Cancer Research UK C18281/A19169, National Institute for Health Research (NIHR)

Published
2020
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17. Shared decision making in breast cancer treatment guidelines: Development of a quality assessment tool and a systematic review

Author

Maes-Carballo, Marta, Muñoz-Núñez, Isabel, Martín-Díaz, Manuel, Mignini, Luciano, Bueno-Cavanillas, Aurora, Khan, Khalid Saeed, [Maes-Carballo,M] Department of General Surgery, Complexo Hospitalario de Ourense, Ourense, Spain. [Maes-Carballo,M, Bueno-Cavanillas,A, Khan,KS] Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain. [Muñoz-Núñez,I, Martín-Díaz,M] Department of General Surgery, Hospital de Motril, Granada, Spain. [Mignini,L] Unidad de Mastología de Grupo Oroño, Rosario, Argentina [Bueno-Cavanillas,A, and Khan,KS] CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Bueno-Cavanillas,A] Instituto de Investigación Biosanitaria IBS, Granada, Spain.

Subjects
Breast cancer treatment, Consensus, Neoplasias de la Mama, Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Thinking::Decision Making::Consensus [Medical Subject Headings], Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Thinking::Decision Making [Medical Subject Headings], Guía de práctica clínica, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Breast cancer, Toma de decisiones conjunta, Consenso, Check Tags::Female [Medical Subject Headings], Information Science::Information Science::Communications Media::Publications::Bibliography as Topic::Bibliometrics [Medical Subject Headings], Clinical practice guidelines, Shared decision making, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings]
Abstract

Background: It is not clear whether clinical practice guidelines (CPGs) and consensus statements (CSs) are adequately promoting shared decision making (SDM). Objective: To evaluate the recommendations about SDM in CPGs and CSs concerning breast cancer (BC) treatment. Search strategy: Following protocol registration (Prospero no.: CRD42018106643), CPGs and CSs on BC treatment were identified, without language restrictions, through systematic search of bibliographic databases (MEDLINE, EMBASE, Web of Science, Scopus, CDSR) and online sources (12 guideline databases and 51 professional society websites) from January 2010 to December 2019. Inclusion criteria: CPGs and CSs on BC treatment were selected whether published in a journal or in an online document. Data extraction and synthesis: A 31-item SDM quality assessment tool was developed and used to extract data in duplicate. Main results: There were 167 relevant CPGs (139) and CSs (28); SDM was reported in only 40% of the studies. SDM was reported more often in recent publications after 2015 (42/101 (41.6 %) vs 46/66 (69.7 %), P = .0003) but less often in medical journal publications (44/101 (43.5 %) vs 17/66 (25.7 %), P = .009). In CPGs and CSs with SDM, only 8/66 (12%) met one-fifth (6 of 31) of the quality items; only 14/66 (8%) provided clear and precise SDM recommendations. Discussion and conclusions: SDM descriptions and recommendations in CPGs and CSs concerning BC treatment need improvement. SDM was more frequently reported in CPGs and CSs in recent years, but surprisingly it was less often covered in medical journals, a feature that needs attention. Yes

Published
2020

18. Serum phospholipids fatty acids and breast cancer risk by pathological subtype

Author

Antonio Antón, Beatriz Pérez-Gómez, Manuel Ramos-Vázquez, Inmaculada Criado-Navarro, Blanca Hernando, Angel Guerrero-Zotano, Raquel Andrés, Rosalia Caballero, Antonio Llombart-Cussac, Ana M. Casas, Miguel Martín, José Manuel Baena-Cañada, Begoña Bermejo, Virginia Lope, Montserrat Muñoz, Feliciano Priego-Capote, Ana de Juan, Adela Castelló, José A. García-Sáenz, Marina Pollán, Rosa María Franquesa, Pedro Sánchez-Rovira, Silvia Antolín, Asociación Española Contra el Cáncer, Sociedad Española de Oncología Médica, Ministerio de Economía y Competitividad (España), Federación Española de Cáncer de Mama, Medicina, Fundación Científica AECC, [Lope,V, Pérez-Gómez,B, Castelló,A, Pollán,M] Cancer and Environmental Epidemiology Unit, Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain. [Lope,V, Pollán,M] Consortium for Biomedical Research in Epidemiology & Public Health, CIBERESP, Madrid, Spain. [Lope,V, Guerrero-Zotano,Á, Casas,A, Baena-Cañada,JM, Bermejo,B, Antolí,S, Sánchez-Rovira,P, Ramos-Vázquez,M, Antón,A, García-Saénz,JÁ, Muñoz,M, de Juan,A, Andrés,R, Llombart-Cussac,A, Hernando,B, Franquesa,RM, Caballero,R, Martín,M, Pollán,M] GEICAM Spanish Breast Cancer Group, Madrid, Spain. [Guerrero-Zotano,Á] Instituto Valenciano de Oncología, Valencia, Spain. [Casas,A] Hospital Universitario Virgen Del Rocio, Sevilla, Spain. [Baena-Cañada,JM] Hospital Universitario Puerta del Mar, Cádiz, Spain. [Baena-Cañada,JM] Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Cádiz, Spain. [Bermejo,B] Hospital Clínico Universitario de Valencia, Valencia, Spain. [Bermejo,B] Biomedical Research Institute INCLIVA, Valencia, Spain. [Bermejo,B, Martín,M] CIBERONC, ISCIII, Madrid, Spain. [Criado-Navarro,I, Priego-Capote,F] Analytical Chemistry Department, Universidad de Córdoba, Córdoba, Spain. [Criado-Navarro,I, Priego-Capote,F] Maimónides Institute of Biomedical Research (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain. [Criado-Navarro,I, Priego-Capote,F] CIBERFES, ISCIII, Madrid, Spain. [Antolín,S] Medical Oncology Unit, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain. [Sánchez-Rovira,P] Complejo Hospitalario de Jaén, Jaén, Spain. [Ramos-Vázquez,M] Centro Oncológico de Galicia, A Coruña, Spain. [Antón,A] Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain. [Castell,A] Faculty of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain. [García-Saénz,JÁ] Hospital Clínico San Carlos, Madrid, Spain. [Muñoz,M] Medical Oncology, Hospital Clínic Barcelona, Barcelona, Spain. [Muñoz,M] Translational Genomics and Targeted Therapeutics, Institut d’Investigacions Biomèdiques Pi i Sunyer-IDIBAPS, Barcelona, Spain. [de Juan,A] Hospital Marqués de Valdecilla, Santander, Spain. [Andrés,R] Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain. [Llombart-Cussac,A] Hospital Arnau de Vilanova, Valencia, Spain. [Hernando,B] Hospital General Yagüe, Burgos, Spain. [Franquesa,RM] Hospital General de Vic, Barcelona, Spain. [Martín,M] Hospital General Universitario Gregorio Marañón, Madrid, Spain. [Martín,M] Instituto Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain., and This study was funded by the Fundación Científica Asociación Española Contra el Cancer (AECC) (Scientific Foundation of the Spanish Association against Cancer 2006 & 2016), Sociedad Española de Oncología Médica (SEOM) (Spanish Society of Medical Oncology), Ministerio de Economía y Competitividad (Spanish Ministry of Economy and Coiveness. IJCI-2014-20900), Fundación Cerveza y Salud 2005 (Beer and Health Foundation 2005) and Federación de Asociaciones de Mujeres con Cáncer de Mama (FECMA) (Spanish Federation of Associations of Women with Breast Cancer). This article presents independent research. The views expressed are those of the authors and not necessarily those of the Carlos III Institute of Health.

Subjects
0301 basic medicine, Àcids grassos, Grasas, Gastroenterology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Fats, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, EpiGEICAM, Surveys and Questionnaires, Fosfolípidos, Palmitoleic acid, Ácidos grasos, Phospholipids, desaturation indices, Nutrition and Dietetics, Estudios de casos y controles, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Breast neoplasm, Fatty Acids, Chemicals and Drugs::Lipids::Fatty Acids [Medical Subject Headings], Middle Aged, Elaidic acid, 030220 oncology & carcinogenesis, Neoplasias de la mama, Female, Stearic acid, Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, Pharmacological [Medical Subject Headings], lcsh:Nutrition. Foods and food supply, Adult, Risk, medicine.medical_specialty, fats, Phenomena and Processes::Mathematical Concepts::Probability::Risk [Medical Subject Headings], Linoleic acid, Breast cancer subtypes, Breast Neoplasms, lcsh:TX341-641, Desaturation indices, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Feeding Behavior [Medical Subject Headings], Article, Information Science::Information Science::Data Collection::Questionnaires [Medical Subject Headings], Càncer de mama, 03 medical and health sciences, breast neoplasm, Internal medicine, Biomarkers, Tumor, medicine, Humans, Fatty acids, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Chemicals and Drugs::Lipids::Phospholipids [Medical Subject Headings], Life Style, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], business.industry, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Feeding Behavior, Odds ratio, medicine.disease, Confidence interval, breast cancer subtypes, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], chemistry, Spain, Case-Control Studies, business, Body mass index, Food Science
Abstract

This study evaluates whether serum phospholipids fatty acids (PL-FAs) and markers of their endogenous metabolism are associated with breast cancer (BC) subtypes. EpiGEICAM is a Spanish multicenter matched case-control study. A lifestyle and food frequency questionnaire was completed by 1017 BC cases and healthy women pairs. Serum PL-FA percentages were measured by gas chromatography-mass spectrometry. Conditional and multinomial logistic regression models were used to quantify the association of PL-FA tertiles with BC risk, overall and by pathological subtype (luminal, HER2+ and triple negative). Stratified analyses by body mass index and menopausal status were also performed. Serum PL-FAs were measured in 795 (78%) pairs. Women with high serum levels of stearic acid (odds ratio (OR)T3vsT1 = 0.44, 95% confidence interval (CI) = 0.30&ndash, 0.66), linoleic acid (ORT3vsT1 = 0.66, 95% CI = 0.49&ndash, 0.90) and arachidonic to dihomo-&gamma, linolenic acid ratio (OR T3vsT1 = 0.64, 95% CI = 0.48&ndash, 0.84) presented lower BC risk. Participants with high concentrations of palmitoleic acid (ORT3vsT1 = 1.65, 95% CI = 1.20&ndash, 2.26), trans-ruminant palmitelaidic acid (ORT3vsT1 = 1.51, 95% CI = 1.12&ndash, 2.02), trans-industrial elaidic acid (ORT3vsT1 = 1.52, 95% CI = 1.14&ndash, 2.03), and high oleic to stearic acid ratio (ORT3vsT1 = 2.04, 95% CI = 1.45&ndash, 2.87) showed higher risk. These associations were similar in all BC pathological subtypes. Our results emphasize the importance of analyzing fatty acids individually, as well as the desaturase activity indices.

Published
2020

19. GEICAM Guidelines for the Management of Patients with Breast Cancer During the COVID-19 Pandemic in Spain

Author

Martín, Miguel, Guerrero-Zotano, Ángel, Montero, Ángel, Jara, Carlos, Filipovich, Elena, Rojo, Federico, Moreno, Fernando, García-Sáenz, Jose Ángel, Alés, Jose Enrique, Chacón, José Ignacio, Cruz, Josefina, Giménez, Julia, Cruz-Merino, Luis, Algara López, Manuel-Ignacio, Santisteban, Marta, López Tarruella, Sara, GEICAM Spanish Breast Cancer Group Steering Committee, GEICAM Spanish Breast Cancer Group Steering Committee, [Martin,M, López Tarruella,S] Medical Oncology, Instituto de Investigación Sanitaria Gregorio Marañón, Departamento de Medicina, Universidad Complutense, Madrid, Spain. [Martin,M, Rojo,F, García-Sáenz,JA, López Tarruella,S] Centro de Investigación Biomedica en Red de Oncologia, CIBERONC-ISCIII, Spain. [Guerrero-Zotano,A] Medical Oncology, Instituto Valenciano de Oncología, Valencia, Spain. [Montero,A] Radiation Oncology, Hospital HM Sanchinarro, Madrid, Spain. [Jara,C] Medical Oncology, Universidad Rey Juan Carlos, Hospital Fundación Alcorcón, Madrid, Spain. [Filipovich,E, Alés,JE] Medical Oncology, Complejo Asistencial de Ávila, Ávila, Spain. [Rojo,F] Pathology, Hospital Fundación Jimenez Díaz de Madrid, Madrid, Spain. [Moreno,F, and García-Sáenz,JA] Medical Oncology, Hospital Universitario Clínico San Carlos de Madrid, Madrid, Spain. [Chacón,JI] Medical Oncology, Hospital Virgen de la Salud de Toledo, Toledo, Spain. [Cruz,J] Medical Oncology, Hospital Universitario de Canarias, Tenerife, Spain. [Gimenez,J] Surgery, Instituto Valenciano de Oncología, Valencia, Spain. [Cruz-Merino,L] Medical Oncology, Hospital Virgen de Macarena de Sevilla, Seville, Spain. [Algara,M] Radiation Oncology, Hospital del Mar de Barcelona, Barcelona, Spain. [Santisteban,M] Medical Oncology, Clínica Universidad de Navarra, Navarra, Spain.

Subjects
Cancer Research, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), España, Clinical Decision-Making, Context (language use), Breast Neoplasms, Medical Oncology, SARS‐CoV‐2, Expert recommendations, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Patient Admission, COVID‐19, Pandemic, Health care, Breast Cancer, medicine, Humans, 030212 general & internal medicine, skin and connective tissue diseases, Intensive care medicine, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Pandemia, business.industry, SARS-CoV-2, Neoplasias de la Mama, Health Care::Environment and Public Health::Public Health::Disease Outbreaks::Epidemics::Pandemics [Medical Subject Headings], Cancer, COVID-19, medicine.disease, Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [Medical Subject Headings], Treatment efficacy, Coronavirus, Oncology, Spain, 030220 oncology & carcinogenesis, Female, business, Delivery of Health Care
Abstract

GEICAM Spanish Breast Cancer Group Steering Committee.-- This article also appears in: COVID-19 and Cancer Article Collection., Breast cancer (BC) is the most common cancer in women in Spain. During the COVID‐19 pandemic caused by the SARS‐CoV‐2 virus, patients with BC still require timely treatment and follow‐up; however, hospitals are overwhelmed with infected patients and, if exposed, patients with BC are at higher risk for infection and serious complications if infected. Thus, health care providers need to evaluate each BC treatment and in‐hospital visit to minimize pandemic‐associated risks while maintaining adequate treatment efficacy. Here we present a set of guidelines regarding available options for BC patient management and treatment by BC subtype in the context of the COVID‐19 pandemic. Owing to the lack of evidence about COVID‐19 infection, these recommendations are mainly based on expert opinion, medical organizations' and societies' recommendations, and some published evidence. We consider this a useful tool to facilitate medical decision making in this health crisis situation we are facing.

Published
2020

20. Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and risk of in situ breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author

Christina C. Dahm, Marc J. Gunter, Carlotta Sacerdote, Carmen Santiuste, Sabine Rohrmann, Merete Ellingjord-Dale, Cecilie Kyrø, Anika Hüsing, Renée T. Fortner, Eva Ardanaz, Antonia Trichopoulou, María Dolores López, Claudia Agnoli, Elisabete Weiderpass, Virginia Menéndez, Rudolf Kaaks, Signe Borgquist, Marina Kvaskoff, Patrick Arveux, Anne Tjønneland, Carlo La Vecchia, Helene Tilma Vistisen, Marije F. Bakker, Antonio Agudo, María José Sánchez, Agnès Fournier, Laure Dossus, Kay-Tee Khaw, Timothy J. Key, Guri Skeie, Eleni Peppa, Rosario Tumino, Elio Riboli, Salma Butt, Carla H. van Gils, Nena Karavasiloglou, Kostantinos K. Tsilidis, Tilman Kühn, Giovanna Masala, Inge Huybrechts, Matthias B. Schulze, Domenico Palli, Anna Karakatsani, Jenny Chang-Claude, Salvatore Panico, Apollo - University of Cambridge Repository, [Karavasiloglou,N, Rohrmann,S] Division of Chronic Disease Epidemiology, Institute for Epidemiology, Biostatistics and Prevention, University of Zurich, Zurich, Switzerland. [Karavasiloglou,N, Rohrmann,S] Cancer Registry Zurich and Zug, University Hospital Zurich, Zurich, Switzerland. [Karavasiloglou,N, Hüsing,A, Turzanski Fortner,R, Chang-Claude,J, Kaaks,R, Kühn,T] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Masala,G, Palli,D] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. [van Gils,CH, Bakker,MF] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. [Huybrechts,I, Weiderpass,E, Dossus,L] International Agency for Research on Cancer, Lyon, France. [Weiderpas,E, Skeie,G] Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Arveux,P, Fournier,A, Kvaskoff,M] CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France. [Arveux,P, Kvaskoff,M] Gustave Roussy, Villejuif, France. [Arveux,P] Breast and Gynaecologic Cancer Registry of Côte d’Or, Georges-François Leclerc Cancer Centre, UNICANCER, Dijon, France. [Tjønneland,A] Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [Tjønneland,A, Kyrø,C] Danish Cancer Society Research Center, Copenhagen, Denmark. [Dahm,CC, Vistisen,HT] Department of Public Health, Aarhus University, Aarhus, Denmark. [Sánchez,MJ] Andalusian School of Public Health (EASP), Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain. [Sánchez,MJ, Chirlaque López,MD, Santiuste,C, Ardanaz,E] CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Sánchez,MJ] Universidad de Granada, Granada, Spain. [Chirlaque López,MD, Santiuste,C] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Chirlaque López,MD] Department of Health and Social Sciences, Murcia University, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Menéndez,V] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer, Catalan Institute of Oncology - ICO, Nutrition and Cancer Group, Bellvitge Biomedical Research Institute - IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Trichopoulou,A, Karakatsani,A, La Vecchia,C, Peppa,E] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] 2nd Pulmonary Medicine Department, School of Medicine, 'ATTIKON' University Hospital, National and Kapodistrian University of Athens, Haidari, Greece. [La Vecchia,C] Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. [Agnoli,C] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Panico,S] Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Department, Azienda Sanitaria Provinciale (ASP), Ragusa, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy. [Butt,ST] Department of Clinical Sciences, Lund University, Malmö, Sweden. [Butt,ST] Department of Surgery, Skåne University Hospital, Malmö, Sweden. [Borgquist,S] Department of Oncology, Aarhus University Hospital, Aarhus University, Aarhus, Denmark. [Borgquist,S] Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden. [Skeie,G] Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK. [Schulze,M] Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany. [Key,T] Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Khaw,KT] Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Tsilidis,KK, Ellingjord-Dale,M, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., The coordination of the European Prospective Investigation into Cancer and Nutrition (EPIC) is supported financially by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (France), German Cancer Aid, German Cancer Research Center (German Cancer Research Center), Federal Ministry of Education and Research (Federal Ministry of Education and Research), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (Ministry of Health, Welfare and Sport), Netherlands Cancer Registry (Netherlands Cancer Registry), LK Research Funds, Dutch Prevention Funds, Dutch Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands (the Netherlands), Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), the Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO, Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK)., Tjønneland, Anne [0000-0003-4385-2097], Dahm, Christina C [0000-0003-0481-2893], Tumino, Rosario [0000-0003-2666-414X], and Borgquist, Signe [0000-0001-7938-8893]

Subjects
0301 basic medicine, Male, Breastfeeding, lcsh:Medicine, Breast carcinoma in situ, GUIDELINES, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, 0302 clinical medicine, Breast cancer, Risk Factors, Medicine, Prospective Studies, Prospective cohort study, 11 Medical and Health Sciences, Medicine(all), Geographical Locations::Geographic Locations::Americas::North America::United States [Medical Subject Headings], Hazard ratio, Academies and Institutes, Cohort, General Medicine, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Lifestyle Score, Europe, POSTMENOPAUSAL WOMEN, 030220 oncology & carcinogenesis, Female, CONCORDANCE, Life Sciences & Biomedicine, PROJECT, In situ breast cancer, Cohort study, Research Article, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Estudios de cohortes, RECREATIONAL PHYSICAL-ACTIVITY, Check Tags::Male [Medical Subject Headings], Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Data Collection::Nutrition Assessment [Medical Subject Headings], Breast Neoplasms, Estilo de vida, Càncer de mama, 03 medical and health sciences, Medicine, General & Internal, Medicina preventiva, DIETARY, General & Internal Medicine, Journal Article, Humans, VDP::Medisinske Fag: 700, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Carcinoma de mama in situ, Preventive medicine, 030109 nutrition & dietetics, Cancer prevention, Science & Technology, business.industry, Prevention, lcsh:R, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], medicine.disease, Lifestyle, United States, VDP::Medical disciplines: 700, Nutrition Assessment, Health Care::Health Care Economics and Organizations::Organizations::Academies and Institutes [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer research, Life style, Geographical Locations::Geographic Locations::Europe [Medical Subject Headings], business
Abstract

Background Even though in situ breast cancer (BCIS) accounts for a large proportion of the breast cancers diagnosed, few studies have investigated potential risk factors for BCIS. Their results suggest that some established risk factors for invasive breast cancer have a similar impact on BCIS risk, but large population-based studies on lifestyle factors and BCIS risk are lacking. Thus, we investigated the association between lifestyle and BCIS risk within the European Prospective Investigation into Cancer and Nutrition cohort. Methods Lifestyle was operationalized by a score reflecting the adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations. The recommendations utilized in these analyses were the ones pertinent to healthy body weight, physical activity, consumption of plant-based foods, energy-dense foods, red and processed meat, and sugary drinks and alcohol, as well as the recommendation on breastfeeding. Cox proportional hazards regression was used to assess the association between lifestyle score and BCIS risk. The results were presented as hazard ratios (HR) and corresponding 95% confidence intervals (CI). Results After an overall median follow-up time of 14.9 years, 1277 BCIS cases were diagnosed. Greater adherence to the WCRF/AICR cancer prevention recommendations was not associated with BCIS risk (HR = 0.98, 95% CI 0.93–1.03; per one unit of increase; multivariable model). An inverse association between the lifestyle score and BCIS risk was observed in study centers, where participants were recruited mainly via mammographic screening and attended additional screening throughout follow-up (HR = 0.85, 95% CI 0.73–0.99), but not in the remaining ones (HR = 0.99, 95% CI 0.94–1.05). Conclusions While we did not observe an overall association between lifestyle and BCIS risk, our results indicate that lifestyle is associated with BCIS risk among women recruited via screening programs and with regular screening participation. This suggests that a true inverse association between lifestyle habits and BCIS risk in the overall cohort may have been masked by a lack of information on screening attendance. The potential inverse association between lifestyle and BCIS risk in our analyses is consistent with the inverse associations between lifestyle scores and breast cancer risk reported from previous studies.

Published
2019
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21. Prospective analysis of circulating metabolites and breast cancer in EPIC

Author

José María Huerta, Salvatore Panico, Antonia Trichopoulou, Joseph A. Rothwell, Sabina Sieri, Anja Olsen, Christina C. Dahm, Ruth C. Travis, Audrey Gicquiau, Pilar Amiano, Elisabete Weiderpass, N. Charlotte Onland-Moret, Antonio Agudo, Anna Karakatsani, Isabelle Romieu, Paolo Vineis, Mathilde His, Elio Riboli, Marc J. Gunter, Guri Skeie, Tilman Kühn, Augustin Scalbert, Carla H. van Gils, Georgia Martimianaki, Therese Haugdahl Nøst, Anne Tjønneland, Heiner Boeing, Laure Dossus, Pietro Ferrari, Julie A. Schmidt, Rosario Tumino, Konstantinos K. Tsilidis, David Achaintre, Torkjel M. Sandanger, Agnès Fournier, Sofia Christakoudi, María José Sánchez, Vivian Viallon, Renée T. Fortner, Kim Overvad, Giovanna Masala, Sabina Rinaldi, J. Ramón Quirós, Gianluca Severi, Eva Ardanaz, [His,M, Viallon,V, Dossus,L, Gicquiau,A, Achaintre,D, Scalbert,A, Ferrari,P, Weiderpass,E, Gunter,MJ, Rinaldi,S] International Agency for Research on Cancer, Lyon, France. [Romieu,I] Centre for Research on Population Health, National Institute of Public Health, Cuernavaca, Mexico. [Onland-Moret,NC, van Gils,CH] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. [Dahm,CC, Overvad,K] Department of Public Health, Aarhus University, Aarhus, Denmark. [Overvad,K] Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. [Olsen,A, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Tjønneland,A] University of Copenhagen, Copenhagen, Denmark. [Fournier,A, Rothwell,JA, Severi,G] CESP, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France. [Fournier,A, Severi,G] Gustave Roussy, Villejuif, France. [Kühn,T, Fortner,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Trichopoulou,A, Karakatsani,A, Martimianaki,G] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, 'ATTIKON' University Hospital, Haidari, Greece. [Masala,G] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network – ISPRO, Florence, Italy. [Sieri,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Department, 'M.P.Arezzo'Hospital, ASP Ragusa, Ragusa, Italy. [Vineis,P] Italian Institute for Genomic Medicine (IIGM), Turin, Italy. [Vineis,P] MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. [Panico,S] Dipartimento di medicina clinica e chirurgia, Federico II University, Naples, Italy. [Nøst,TH, Sandanger,TM, Skeie,G] Department of Community Medicine, UiT the Arctic University of Norway, Tromso, Norway. [Skeie,G] Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Universidad de Granada, Granada, Spain. [Sánchez,MJ, Amiano,P, Huerta,JM, Ardanaz,E] CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Schmidt,JA, Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Riboli,E, Tsilidis,KK, Christakoudi,S] Department of Epidemiology and Biostatistics, Imperial College London, St Mary’s Campus, Norfolk Place, London, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Christakoudi,S] MRC Centre for Transplantation, King’s College London, Great Maze Pond, London, SE1 9RT, UK, This work was funded by the French National Cancer Institute (grant number 2015-166). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), European Research Council (ERC-2009-AdG 232997), and Nordforsk, Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra, and the CERCA Program (Generalitat de Catalunya) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).

Subjects
0301 basic medicine, Oncology, lcsh:Medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Mass Spectrometry, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, 0302 clinical medicine, Breast cancer, Information Science::Information Science::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Risk Factors, Estudios prospectivos, Prospective Studies, Prospective cohort study, 11 Medical and Health Sciences, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], education.field_of_study, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Incidence, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Metabolomics [Medical Subject Headings], General Medicine, Metabolómica, Middle Aged, metabolomics, 3. Good health, Research Design, 030220 oncology & carcinogenesis, Cohort, Neoplasias de la mama, Female, Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, Pharmacological [Medical Subject Headings], Cohort study, Research Article, prospective study, Adult, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Population, Breast Neoplasms, Càncer de mama, 03 medical and health sciences, breast cancer, Internal medicine, Cell Line, Tumor, General & Internal Medicine, medicine, Journal Article, Metabolomics, Humans, Prospective study, education, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, business.industry, lcsh:R, Case-control study, Cancer, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Odds ratio, medicine.disease, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Case-Control Studies, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Mass Spectrometry [Medical Subject Headings], Biomarkers
Abstract

BackgroundMetabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk.MethodsA nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression.ResultsAmong women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70–0.90), asparagine (OR = 0.83 (0.74–0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76–0.90)), aa C36:3 (OR = 0.84 (0.77–0.93)), ae C34:2 (OR = 0.85 (0.78–0.94)), ae C36:2 (OR = 0.85 (0.78–0.88)), and ae C38:2 (OR = 0.84 (0.76–0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11–1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06–1.24)) and PC ae C36:3 (OR = 0.88 (0.82–0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity.ConclusionsThese findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.

Published
2019
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22. Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy

Author

Francisco G. Ortega, Christian Rolfo, José Expósito, Diego de Miguel-Pérez, Jose L. Garcia-Puche, Alba Rodríguez-Martínez, Jordi Martorell-Marugán, María del Carmen Garrido-Navas, Marta Legueren, María José Serrano, José A. Lorente, Inmaculada Robles-Fernandez, Hugh Ilyine, Pedro Carmona-Sáez, [Rodriguez-Martinez,A, de Miguel-Perez,D, Ortega,FG, Garcia-Puche,JL, Robles-Fernandez,I, Garrido-Navas,MC, Lorente,JA, Serrano,MJ] Liquid biopsy and metastasis research group, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government PTS, Granada, Spain. [Rodriguez-Martinez,A, Lorente,JA] Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Faculty of Medicine, University of Granada, Spain. [García-Puche,JL, Exposito,J, Legueren,M, Serrano,MJ] Comprehensive oncology division, Clinical University Hospital, Virgen de las Nieves-San Cecilio, Granada, Spain. [Martorell-Marugan,J, Carmona-Sáez,P] Bioinformatics Unit, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government PTS. Granada, Spain. [Rolfo,C] Thoracic Medical Oncology, Early Clinical Trials, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC), Baltimore, USA. [Ilyine,H] DestiNA Genomics Ltd, Edinburgh, UK., and This work was supported by 'Granada Research of Excellence Initiative on BioHealth (GREIB)', the PhD grant from the University of Granada and the PhD grant from the Spanish Government (FPU) 2014, REF FPU14/05461.

Subjects
Oncology, medicine.medical_treatment, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Feasibility Studies [Medical Subject Headings], Exosomes, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy [Medical Subject Headings], Anatomy::Body Regions::Breast [Medical Subject Headings], Exosomas, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Localized breast cancer, 0302 clinical medicine, Circulating tumor cell, Surgical oncology, Positron Emission Tomography Computed Tomography, Medicine, Breast, Prospective Studies, Neoadjuvant therapy, Anatomy::Cells::Neoplastic Cells, Circulating [Medical Subject Headings], microRNA, Diagnóstico, Conservative surgery, Pronóstico, MicroRNA, Cancer diagnosis, Middle Aged, Progesterone Receptor Status, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Neoplastic Cells, Circulating, Prognosis, Metastatic breast cancer, Neoadjuvant Therapy, Treatment Outcome, 030220 oncology & carcinogenesis, Neoplasias de la mama, Female, Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Cytoplasmic Vesicles::Transport Vesicles::Exosomes [Medical Subject Headings], Research Article, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Antineoplastic Agents, Breast Neoplasms, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression Profiling [Medical Subject Headings], lcsh:RC254-282, Neoadjuvant chemotherapy, 03 medical and health sciences, Breast cancer, Terapia neoadyuvante, Internal medicine, Biomarkers, Tumor, Humans, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings], Chemotherapy, Cancer prognosis, business.industry, Gene Expression Profiling, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [Medical Subject Headings], Liquid Biopsy, Circulating tumor cells, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], medicine.disease, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [Medical Subject Headings], MicroRNAs, Check Tags::Female [Medical Subject Headings], Feasibility Studies, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], business, Células neoplásicas circulantes
Abstract

Background: Breast cancer patients under neoadjuvant chemotherapy includes a heterogeneous group of patients who eventually develop distal disease, not detectable by current methods. We propose the use of exosomal miRNAs and circulating tumor cells as diagnostic and predictive biomarkers in these patients. Methods: Fifty-three breast cancer women initially diagnosed with localized breast cancer under neoadjuvant chemotherapy were prospectively enrolled in this study. However, six of them were later re-evaluated and diagnosed as metastatic breast cancer patients by PET-CT scan. Additionally, eight healthy donors were included. Circulating tumor cells and serum exosomal miRNAs were isolated from blood samples before and at the middle of neoadjuvant therapy and exosomal miRNA levels analyzed by qPCR. Results: Before neoadjuvant therapy, exosomal miRNA-21 and 105 expression levels were higher in metastatic versus non-metastatic patients and healthy donors. Likewise, higher levels of miRNA-222 were observed in basal-like (p = 0.037) and in luminal B versus luminal A (p = 0.0145) tumor subtypes. Exosomal miRNA-222 levels correlated with clinical and pathological variables such as progesterone receptor status (p = 0.017) and Ki67 (p = 0.05). During neoadjuvant treatment, exosomal miRNA-21 expression levels directly correlated with tumor size (p = 0.039) and inversely with Ki67 expression (p = 0.031). Finally, higher levels of exosomal miRNA-21, miRNA-222, and miRNA-155 were significantly associated with the presence of circulating tumor cells. Conclusion: Liquid biopsies based on exosomal miRNAs and circulating tumor cells can be a complementary clinical tool for improving breast cancer diagnosis and prognosis., This work was supported by “Granada Research of Excellence Initiative on BioHealth (GREIB)”, the PhD grant from the University of Granada and the PhD grant from the Spanish Government (FPU) 2014, REF FPU14/05461

Published
2019

23. Association of breast and gut microbiota dysbiosis and the risk of breast cancer: a case-control clinical study

Author

María Teresa Sánchez-Barrón, Ana I. Álvarez-Mercado, Carmen M Ruiz-Marín, Cándido Robles-Sánchez, Saturnino Reyes Lartategui, María José Sáez-Lara, María Belén Sánchez-Andujar, Mariana F. Fernández, Alejandro J. Pérez-Alonso, Ana Moreno-Delgado, Tania Gallart-Aragón, Natalia Chueca, Katia Torres-Martínez, Julio Plaza-Díaz, Federico García, Iris Reina-Pérez, Luis Fontana, Pablo Torné, [Plaza-Díaz,J, Álvarez-Mercado,AI, Robles-Sánchez,C, Fontana,L] Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071, Granada, Spain. [Plaza-Díaz,J, Sáez-Lara,MJ, Fontana,L] Institute of Nutrition and Food Technology 'José Mataix', Biomedical Research Center, Parque Tecnológico Ciencias de la Salud, University of Granada, Granada, Spain. [Plaza-Díaz,J, García,F, Chueca,N, Fernández,MF, Fontana,L] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Plaza-Díaz,J] Spanish Consortium for Research on Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. [Ruiz-Marín,CM, Pérez-Alonso,AJ, Sánchez-Andujar,MB] Unit of Mammary Pathology, General Surgery Service, University Hospital of Jaén, Jaén, Spain. [Reina-Pérez,I, Fernández,MF] Department of Radiology, School of Medicine, University of Granada, Granada, Spain. [Fernández,MF] Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain. [Pérez-Alonso,AJ, Torné,P] Department of Surgery, School of Medicine, University of Granada, Granada, Spain. [Torné,P, Gallart-Aragón,T, Sánchez-Barrón,MT, Reyes Lartategui,S] Unit of Mammary Pathology, General Surgery Service, University Hospital Campus de la Salud, Granada, Spain. [García,F, Chueca,N] Department of Microbiology, University Hospital Campus de la Salud, Granada, Spain. [Moreno-Delgado,A, Torres-Martínez,K] Clínica Ana Moreno, Calle Doctor Alejandro Otero, Granada, Spain. [Sáez-Lara,MJ] Department of Biochemistry and Molecular Biology I, School of Sciences, University of Granada, Granada, Spain. [Fernández,MF] Laboratory 207, Biomedical Research Center, Parque Tecnológico Ciencias de la Salud, Granada, Spain., and Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP) of the Institute of Health Carlos III -supported by European Regional Development Fund/FEDER (FIS-PI16/01812) (to MFF)

Subjects
0301 basic medicine, Cancer Research, medicine.medical_treatment, Biopsy, Physiology, Disease, Gut flora, Hongos, Metastasis, Anatomy::Body Regions::Breast [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Study Protocol, Feces, 0302 clinical medicine, Breast cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Biopsy [Medical Subject Headings], Surveys and Questionnaires, Breast, Breast augmentation, Neoadjuvant therapy, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Phenomena and Processes::Metabolic Phenomena::Metabolome [Medical Subject Headings], biology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Microbioma sastrointestinal, Organisms::Viruses [Medical Subject Headings], Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Health Care::Environment and Public Health::Public Health::Environmental Pollution::Environmental Exposure [Medical Subject Headings], Environmental pollutants, Virus, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Estrogens [Medical Subject Headings], Oncology, 030220 oncology & carcinogenesis, Neoplasias de la mama, Metabolome, Breast microbiota, Female, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Dysbiosis [Medical Subject Headings], Disruptores endocrinos, Adult, Anatomy::Fluids and Secretions::Feces [Medical Subject Headings], Breast Neoplasms, Gut microbiota, lcsh:RC254-282, 03 medical and health sciences, Genetics, medicine, Humans, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Endocrine disruptors, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Organisms::Archaea [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Damage [Medical Subject Headings], Bacteria, business.industry, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Endocrine Disruptors [Medical Subject Headings], Fungi, Cancer, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Estrogens, Environmental Exposure, medicine.disease, biology.organism_classification, Archaea, Organisms::Eukaryota::Fungi [Medical Subject Headings], Gastrointestinal Microbiome, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Case-Control Studies, Dysbiosis, business, Contaminantes ambientales, DNA Damage
Abstract

We would like to thank M Luisa Puertas-Martin and Isabel Manzano-Jimenez, nurses at the Unit of Mammary Pathology, General Surgery Service, San Cecilio University Hospital (Granada), without whose enthusiasm the enrolment of participants in Granada would still be stalled. We are indebted to all the women taking part in the study., The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Trial registration ClinicalTrials.gov NCT03885648, 03/25/2019. Retrospectively registered., Background Breast cancer ranks first in women, and is the second cause of death in this gender. In addition to genetics, the environment contributes to the development of the disease, although the factors involved are not well known. Among the latter is the influence of microorganisms and, therefore, attention is recently being paid to the mammary microbiota. We hypothesize that the risk of breast cancer could be associated with the composition and functionality of the mammary/gut microbiota, and that exposure to environmental contaminants (endocrine disruptors, EDCs) might contribute to alter these microbiota. Methods We describe a case-control clinical study that will be performed in women between 25 and 70 years of age. Cases will be women diagnosed and surgically intervened of breast cancer (stages I and II). Women with antecedents of cancer or advanced tumor stage (metastasis), or who have received antibiotic treatment within a period of 3 months prior to recruitment, or any neoadjuvant therapy, will be excluded. Controls will be women surgically intervened of breast augmentation or reduction. Women with oncological, gynecological or endocrine history, and those who have received antibiotic treatment within a period of 3 months prior to recruitment will also be excluded. Blood, urine, breast tissue and stool samples will be collected. Data regarding anthropometric, sociodemographic, reproductive history, tumor features and dietary habits will be gathered. Metabolomic studies will be carried out in stool and breast tissue samples. Metagenomic studies will also be performed in stool and breast tissue samples to ascertain the viral, fungal, bacterial and archaea populations of the microbiota. Quantitation of estrogens, estrogen metabolites and EDCs in samples of serum, urine and breast tissue will also be performed. Discussion: This is the first time that the contribution of bacteria, archaea, viruses and fungi together with their alteration by environmental contaminants to the risk of breast cancer will be evaluated in the same study. Results obtained could contribute to elucidate risk factors, improve the prognosis, as well as to propose novel intervention studies in this disease., This work is funded by grants PI-0538-2017 (Junta de Andalucía, Spain, to LF) and Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP) of the Institute of Health Carlos III -supported by European Regional Development Fund/FEDER (FIS-PI16/01812) (to MFF).

Published
2019
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24. Osteoprotegerin and breast cancer risk by hormone receptor subtype: A nested case-control study in the EPIC cohort

Author

Miren Dorronsoro, Marc J. Gunter, Mathilde His, Helena Schock, Sabina Sieri, Maria Dolores Chirlaque, Aurélie Affret, Rudolf Kaaks, Elisabete Weiderpass, H. Bas Bueno-de-Mesquita, Philippos Orfanos, Melissa A. Merritt, Anne Tjønneland, Domenico Palli, J. Ramón Quirós, María José Sánchez, Theron Johnson, Danja Sarink, Eva Ardanaz, Antonio Agudo, Renée T. Fortner, Laure Dossus, Timothy J. Key, Kim Overvad, Rosario Tumino, Androniki Naska, Petra H.M. Peeters, Heiner Boeing, Amalia Mattiello, Anja Olsen, Sabina Rinaldi, Eiliv Lund, Antonia Trichopoulou, Carla H. van Gils, Marie-Christine Boutron-Ruault, Kay-Tee Khaw, Elio Riboli, Fulvio Ricceri, Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, University Medical Center Utrecht, Imperial College Trust, [Fortner,RT, Sarink,D, Schock,H, Johnson,T, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Tjønneland,A, Olsen,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Affret,A, His,M, Boutron-Ruault,MC] Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France. [Affret,A, Boutron-Ruault,MC] Villejuif, France. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Naska,A, Orfanos,P] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Orfanos,P] WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Palli,D] Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy. [Sieri,S] Epidemiology and Prevention Unit, Department of Preventive & Predictive Medicine Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Mattiello,A] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.p.Arezzo' Hospital, ASP Ragusa, Italy. [Ricceri,F] Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco (TO), Italy. [Ricceri,F] Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, Turin, Italy. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB, Merritt,MA, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Bueno-de-Mesquita,HB] Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Peeters,PH, Van Gils,CH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands. [Peeters,PH] MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK. [Weiderpass,E, Lund,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway. [Weiderpass,E] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [Weiderpass,E] Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer. Cancer Epidemiology Research Program. Catalan Institute of Oncology-IDIBELL. L'Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs. GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sánchez,MJ, Chirlaque,MD, Ardanaz,E] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Chirlaque,MD] Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Chirlaque,MD] Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia Research Institute CIBERESP, Basque Regional Health Department, San Sebastian, Spain. [Key,T] Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Khaw,KT] Cancer Epidemiology Unit, University of Cambridge, Cambridge, UK. [Rinaldi,S, Dossus,L, Gunter,M] International Agency for Research on Cancer, Lyon, France., This project was funded by research grant 111454 from the Deutsche Kresbshilfe. RT Fortner was supported by a Marie Curie International Incoming Fellowship of the European Commission’s Seventh Framework Programme (MC-IIF-623984). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, and ISCIII RETIC (RD06/0020) (Spain), the Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK).

Subjects
0301 basic medicine, Oncology, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone [Medical Subject Headings], Estrogen receptor, Progesterone receptor, Cohort Studies, 0302 clinical medicine, Breast cancer, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Receptor Activator of Nuclear Factor-kappa B [Medical Subject Headings], Risk Factors, Prospective Studies, Prospective cohort study, Medicine(all), Osteoprotegerina, biology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, 11 Medical And Health Sciences, General Medicine, Middle Aged, Necrosi, 3. Good health, European Prospective Investigation into Cancer and Nutrition, RANK axis, RANKL, 030220 oncology & carcinogenesis, Neoplasias de la mama, Female, Research Article, musculoskeletal diseases, medicine.medical_specialty, Receptores estrogénicos, Health Care::Environment and Public Health::Public Health::Epidemiologic Factors::Causality::Risk Factors [Medical Subject Headings], Breast Neoplasms, Receptores de progesterona, Receptores de hormonas, Hormone receptor, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [Medical Subject Headings], Càncer de mama, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Necrosis, 03 medical and health sciences, Osteoprotegerin, General & Internal Medicine, Internal medicine, Journal Article, medicine, Humans, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], business.industry, Case-control study, medicine.disease, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Prospective Studies [Medical Subject Headings], 030104 developmental biology, Endocrinology, Case-Control Studies, Nested case-control study, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Climacteric::Menopause::Postmenopause [Medical Subject Headings], biology.protein, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Tumor Necrosis Factor Decoy Receptors::Osteoprotegerin [Medical Subject Headings], VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract

All Author: Renée T. Fortner, Danja Sarink, Helena Schock, Theron Johnson, Anne Tjønneland, Anja Olsen, Kim Overvad, Aurélie Affret, Mathilde His, Marie-Christine Boutron-Ruault, Heiner Boeing, Antonia Trichopoulou, Androniki Naska, Philippos Orfanos, Domenico Palli, Sabina Sieri, Amalia Mattiello, Rosario Tumino, Fulvio Ricceri, H. Bas Bueno-de-Mesquita, Petra H. M. Peeters, Carla H. Van Gils, Elisabete Weiderpass, Eiliv Lund, J. Ramón Quirós, Antonio Agudo, Maria-José Sánchez, María-Dolores Chirlaque, Eva Ardanaz, Miren Dorronsoro, Tim Key, Kay-Tee Khaw, Sabina Rinaldi, Laure Dossus, Marc Gunter, Melissa A. Merritt, Elio Riboli and Rudolf Kaaks, Background: Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Circulating OPG and breast cancer risk has been examined in only one prior study. Methods: A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 2008 incident invasive breast cancer cases (estrogen receptor (ER)+, n = 1622; ER–, n = 386), matched 1:1 to controls, were included in the analysis. Women were predominantly postmenopausal at blood collection (77%); postmenopausal women included users and non-users of postmenopausal hormone therapy (HT). Serum OPG was quantified with an electrochemiluminescence assay. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Results: The associations between OPG and ER+ and ER– breast cancer differed significantly. Higher concentrations of OPG were associated with increased risk of ER– breast cancer (top vs. bottom tertile RR = 1.93 [95% CI 1.24–3.02]; ptrend = 0.03). We observed a suggestive inverse association for ER+ disease overall and among women premenopausal at blood collection. Results for ER– disease did not differ by menopausal status at blood collection (phet = 0.97), and we observed no heterogeneity by HT use at blood collection (phet ≥ 0.43) or age at breast cancer diagnosis (phet ≥ 0.30). Conclusions: This study provides the first prospective data on OPG and breast cancer risk by hormone receptor subtype. High circulating OPG may represent a novel risk factor for ER– breast cancer., This project was funded by research grant 111454 from the Deutsche Kresbshilfe. RT Fortner was supported by a Marie Curie International Incoming Fellowship of the European Commission’s Seventh Framework Programme (MC-IIF-623984). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and the National Research Council (Italy); the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, and ISCIII RETIC (RD06/0020) (Spain); the Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden); and Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK).

Published
2017
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25. Geographical and Temporal Variations in Female Breast Cancer Mortality in the Municipalities of Andalusia (Southern Spain)

Author

Carmen Montaño-Remacha, José María Mayoral-Cortés, Ricardo Ocaña-Riola, [Ocaña-Riola,R] Escuela Andaluza de Salud Pública, Spain. [Ocaña-Riola,R] Instituto de Investigación Biosanitaria de Granada, Spain. [Montaño-Remacha,C, Mayoral-Cortés,JM] Servicio de Epidemiología y Salud Laboral, Dirección General de Salud Pública y Ordenación Farmacéutica, Secretaría General de Salud Pública y Consumo, Consejería de Salud de la Junta de Andalucía, Spain., [Ocana-Riola, Ricardo] Escuela Andaluza Salud Publ, Cuesta Observ 4, Granada 18011, Spain, [Ocana-Riola, Ricardo] Inst Invest Biosanitaria Granada, Doctor Azpitarte 4,4 Planta, Granada 18012, Spain, [Montano-Remacha, Carmen] Consejeria Salud Junta Andalucia, Secretaria Gen Salud Publ & Consumo, Direcc Gen Salud Publ & Ordenac Farmaceut, Serv Epidemiol & Salud Laboral, Ave Innovac S-N,Edificio Arena 1, Seville 41020, Spain, and [Mayoral-Cortes, Jose Maria] Consejeria Salud Junta Andalucia, Secretaria Gen Salud Publ & Consumo, Direcc Gen Salud Publ & Ordenac Farmaceut, Serv Epidemiol & Salud Laboral, Ave Innovac S-N,Edificio Arena 1, Seville 41020, Spain

Subjects
Health, Toxicology and Mutagenesis, España, Bayesian analysis, lcsh:Medicine, Rate ratio, spatial statistics, 0302 clinical medicine, Breast cancer, 030212 general & internal medicine, Patterns, Andalusia, Aged, 80 and over, Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], education.field_of_study, Geography, Spatial statistics, Mortality rate, small areas, Middle Aged, Europe, Trend analysis, Health, Information Science::Information Science::Information Storage and Retrieval::Databases as Topic::Databases, Factual::Geographic Information Systems [Medical Subject Headings], 030220 oncology & carcinogenesis, Neoplasias de la mama, Female, Seasons, Adult, Adolescent, Population, Sistemas de Información Geográfica, Breast Neoplasms, Spatial distribution, Article, Geographical Information System, Young Adult, 03 medical and health sciences, breast cancer, medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Bayes Theorem [Medical Subject Headings], Humans, Teorema de Bayes, Mortality, education, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Female breast cancer, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], lcsh:R, Public Health, Environmental and Occupational Health, Ecological study, Bayes Theorem, medicine.disease, mortality, Small areas, Check Tags::Female [Medical Subject Headings], Spain, Disciplines and Occupations::Natural Science Disciplines::Earth Sciences::Geography [Medical Subject Headings], Mortalidad, trend analysis, Trends, Demography
Abstract

The last published figures have shown geographical variations in mortality with respect to female breast cancer in European countries. However, national health policies need a dynamic image of the geographical variations within the country. The aim of this paper was to describe the spatial distribution of age-specific mortality rates from female breast cancer in the municipalities of Andalusia (southern Spain) and to analyze its evolution over time from 1981 to 2012. An ecological study was devised. Two spatio-temporal hierarchical Bayesian models were estimated. One of these was used to estimate the age-specific mortality rate for each municipality, together with its time trends, and the other was used to estimate the age-specific rate ratio compared with Spain as a whole. The results showed that 98% of the municipalities exhibited a decreasing or a flat mortality trend for all the age groups. In 2012, the geographical variability of the age-specific mortality rates was small, especially for population groups below 65. In addition, more than 96.6% of the municipalities showed an age-specific mortality rate similar to the corresponding rate for Spain, and there were no identified significant clusters. This information will contribute towards a reflection on the past, present and future of breast cancer outcomes in Andalusia Yes

Published
2016

26. Radiation-induced breast angiosarcoma: a case report

Author

Sara Pabón-Fernández, Manolo La Calle-Marcos, Diego Núñez-García, Rosa Albalat-Fernández, Sara Tato-Varela, [Tato-Varela,s, Albalat-Fernández,R, and La Calle-Marcos,M] Clinical Management Unit of Gynaecology and Obstetrics, Hospital Universitario Virgen Macarena, Seville, Spain. [Pabón-Fernández,S] Pathological Anatomy Service, Hospital Universitario Virgen Macarena, Seville, Spain. [Núñez-García,D] Family and Community Medicine, Hospital Universitario Virgen Macarena, Seville, Spain.

Subjects
Cancer Research, medicine.medical_specialty, Neoplasias inducidas por radiación, medicine.medical_treatment, Hemangiosarcoma, Radiation induced, Case Report, Secondary angiosarcoma, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 03 medical and health sciences, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Sarcoma::Hemangiosarcoma [Medical Subject Headings], 0302 clinical medicine, Breast cancer, breast cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Reconstructive Surgical Procedures::Mammaplasty [Medical Subject Headings], medicine, breast reconstruction, Breast reconstruction, Diseases::Neoplasms::Neoplasms, Radiation-Induced [Medical Subject Headings], Anodyne, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Radiation, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Mortality::Survival Rate [Medical Subject Headings], business.industry, Incidence (epidemiology), Breast angiosarcoma, Analgésicos, medicine.disease, Surgery, Radiation therapy, radiation, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Peripheral Nervous System Agents::Sensory System Agents::Analgesics [Medical Subject Headings], Oncology, Mamoplastia, 030220 oncology & carcinogenesis, Neoplasias de la mama, secondary angiosarcoma, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], 030211 gastroenterology & hepatology, Radiology, business
Abstract

Radiation-induced breast angiosarcoma is a severe but rare late complication in the breast-preserving management of breast cancer through surgery and radiotherapy [1]. Often the initial diagnosis of this entity is complex given its relatively anodyne nature and usually being present in the form of typically multifocal reddish-purple papular skin lesions [2]. Because of the low incidence of this tumour, there is a limited number of studies regarding its optimal therapeutic management [3]. The preferred treatment is aggressive surgical removal and the prognosis is poor with an overall survival rate of 12-20% at five years [4]. Yes

Published
2016

27. The INSIG2 rs7566605 polymorphism is not associated with body mass index and breast cancer risk

Author

Olga M. Sinilnikova, Rudolf Kaaks, Pilar Amiano, Anne Tjønneland, José Ramón Quirós, Eiliv Lund, Daniele Campa, Carla H. van Gils, Göran Hallmans, Kay-Tee Khaw, H. Bas Bueno-de-Mesquita, Anika Hüsing, Sabina Rinaldi, Nicholas J. Wareham, Nathalie Chabbert-Buffet, Kim Overvad, Eva Ardanaz, Sabine Rohrmann, Vittorio Krogh, Federico Canzian, Giovanna Masala, Françoise Clavel-Chapelon, María Dolores Chirlaque, Per Lenner, Carlotta Sacerdote, Esther Molina-Montes, Guy Fagherazzi, Jakob Stegger, James McKay, N. Charlotte Onland-Moret, Salvatore Panico, Rosario Tumino, Afshan Siddiq, Birgit Teucher, Timothy J. Key, Erifili Oustoglou, Ruth C. Travis, Veronique Chajes, Dimosthenis Zylis, Ulla Vogel, Antonia Trichopoulou, Elio Riboli, Nadia Slimani, Heiner Boeing, Núria Sala, Eva Fisher, Wareham, Nicholas [0000-0003-1422-2993], Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, Campa, D, Hüsing, A, Mckay, Jd, Sinilnikova, O, Vogel, U, Tjønneland, A, Overvad, K, Stegger, J, Clavel Chapelon, F, Chabbert Buffet, N, Fagherazzi, G, Trichopoulou, A, Zylis, D, Oustoglou, E, Rohrmann, S, Teucher, B, Fisher, E, Boeing, H, Masala, G, Krogh, V, Sacerdote, C, Panico, Salvatore, Tumino, R, Onland Moret, Nc, van Gils, Ch, Bueno de Mesquita, Hb, Lund, E, Chirlaque, Md, Sala, N, Quirós, Jr, Ardanaz, E, Amiano, P, Molina Montes, E, Hallmans, G, Lenner, P, Travis, Rc, Key, Tj, Wareham, N, Khaw, Kt, Rinaldi, S, Slimani, N, Chajes, V, Siddiq, A, Riboli, E, Kaaks, R, Canzian, F., and [Campa D, Hüssing A, Rohrmann S, Teucher B, Kaaks R, Canzian F] German Cancer Research Center (DKFZ), Heidelberg, Germany. [McKay JD, Slimani N, Chajes V] International Agency for Research on Cancer, Lyon, France. [Sinilnikova O] Hospices Civils de Lyon/Centre Léon Bérard, UMR5201 CNRS-Université Claude Bernard, Lyon, France. [Vogel U] National Food Institute Technical University of Denmark, Denmark. [Tjønneland A] Danish Cancer Society, Copenhagen, Denmark. [Overvad K] Aarhus University Hospital, Aalborg, Denmark. [Stegger J] Department of Cardiology, Cardiovascular Research Centre, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. [Clavel-Chapelon F, Chabbert-Buffet N, Fagherazzi G] Institut Gustave Roussy, Villejuif, France. [Trichopoulou A, Zylis D] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulou A, Oustoglou E] Hellenic Health Foundation, Athens, Greece. [Fisher E, Boeing H] German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany. [Masala G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy. [Krogh V] Istituto Nazionale dei Tumori (IRCCS), Milan, Italy. [Sacerdote C] CPO Piemonte, Turin, Italy. [Panico S] Department of Clinical and Experimental Medicine Federico II University, Naples, Italy. [Tumino R] Azienda Ospedaliera 'Civile M.P.Arezzo' Ragusa, Italy. [Onland-Moret NC, van Gils CH] Julius Center, University Medical Center, Utrecht, The Netherlands. [Bueno-de-Mesquita HB] National Institute for Public Health and the Environment, Bilthoven, The Netherlands. [Lund E] Institute of Community Medicine University of Tromsø, Tromsø, Norway. [Chirlaque MD] Murcia Regional Health Council, Murcia, Spain. [Sala N] Catalan Institute of Oncology, Barcelona, Spain. [Quirós JR] Consejería de Salud y Servicios Sanitarios Principado de Asturias, Oviedo, Spain. [Ardanaz E] Public Health Institute of Navarra, Pamplona, Spain. [Amiano P] Public Health Department of Gipuzkoa, San Sebastian, Spain. [Molina-Montes E] Andalusian School of Public Health, Granada, Spain. [Chirlaque MD, Amiano P, Molina-Montes E] CIBER de Epidemiología y Salud Pública (CIBERESP), Spain. [Hallmans G, Lenner2 P] Umeå University, Umeå, Sweden. [Travis RC, Key TJ] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK OX3 7LF. [Wareham N, Khaw KT] University of Cambridge, Cambridge, UK. [Siddiq A, Riboli E] Imperial College, London, UK.

Subjects
Oncology, Aging, Cancer Research, Genome-wide association study, 32 Biomedical and Clinical Sciences, Body Mass Index, Cohort Studies, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Research Design::Genome-Wide Association Study [Medical Subject Headings], 0302 clinical medicine, 2.1 Biological and endogenous factors, membrane protein, POPULATION, Cancer, 2. Zero hunger, 2 Aetiology, 0303 health sciences, education.field_of_study, Intracellular Signaling Peptides and Proteins, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 4203 Health Services and Systems, 3. Good health, Índice de masa muscular, INSIG2 protein, Adipose Tissue, Neoplasias de la mama, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins [Medical Subject Headings], Female, Life Sciences & Biomedicine, Cohort study, Research Article, Adult, Risk, medicine.medical_specialty, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714, Genotype, Estudios de cohortes, Population, Polimorfismo Genético, COMMON GENETIC VARIANT, PHENOTYPES, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, Breast Neoplasms, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714, lcsh:RC254-282, Estudio de Asociación del Genoma Completo, 03 medical and health sciences, Breast cancer, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], SDG 3 - Good Health and Well-being, Clinical Research, Internal medicine, Breast Cancer, POLYGENIC CONTRIBUTION, medicine, Genetics, Humans, signal peptide, Neoplasm Invasiveness, Obesity, human, education, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], 030304 developmental biology, Nutrition, Aged, Science & Technology, Polymorphism, Genetic, Models, Genetic, business.industry, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, Prevention, Case-control study, 42 Health Sciences, Membrane Proteins, DNA, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic [Medical Subject Headings], medicine.disease, 3211 Oncology and Carcinogenesis, Health Care::Environment and Public Health::Public Health::Epidemiologic Measurements::Biometry::Anthropometry::Body Mass Index [Medical Subject Headings], VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Case-Control Studies, Immunology, INSIG2 protein, human, business, Body mass index, Genome-Wide Association Study
Abstract

Background The single nucleotide polymorphism rs7566605, located in the promoter of the INSIG2 gene, has been the subject of a strong scientific effort aimed to elucidate its possible association with body mass index (BMI). The first report showing that rs7566605 could be associated with body fatness was a genome-wide association study (GWAS) which used BMI as the primary phenotype. Many follow-up studies sought to validate the association of rs7566605 with various markers of obesity, with several publications reporting inconsistent findings. BMI is considered to be one of the measures of choice to evaluate body fatness and there is evidence that body fatness is related with an increased risk of breast cancer (BC). Methods we tested in a large-scale association study (3,973 women, including 1,269 invasive BC cases and 2,194 controls), nested within the EPIC cohort, the involvement of rs7566605 as predictor of BMI and BC risk. Results and Conclusions In this study we were not able to find any statistically significant association between this SNP and BMI, nor did we find any significant association between the SNP and an increased risk of breast cancer overall and by subgroups of age, or menopausal status.

Published
2016
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28. Jaw osteonecrosis management around a dental implant inserted 2 years before starting treatment with zoledronic acid

Author

Alberto Jiménez-Burkhardt, Ana-Belén Marín-Fernández, Blas García Medina, Antonio Aguilar-Salvatierra, Gerardo Gómez-Moreno, [Marín-Fernández,AB, García Medina,B] Oral and Maxillofacial Surgery Service, Virgen de las Nieves University Hospital, Granada, Spain. [Aguilar-Salvatierra,A] Faculty of Dentistry, University of Granada, Granada, Spain. [Jiménez-Burkhardt,A, and Gómez-Moreno,G] Department of Special Care in Dentistry, Faculty of Dentistry, University of Granada, Granada, Spain.

Subjects
Peri-implantitis, Bone disease, medicine.medical_treatment, Difosfonatos, Dentistry, Case Report, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Dental implant, Chemicals and Drugs::Organic Chemicals::Organophosphorus Compounds::Diphosphonates [Medical Subject Headings], Implantes dentales, Anatomy::Cells::Connective Tissue Cells::Macrophages::Osteoclasts [Medical Subject Headings], Imidazoles, Osteonecrosis, Bisphosphonates, Diseases::Neoplasms [Medical Subject Headings], CIENCIAS MÉDICAS [UNESCO], Ciencias de la salud, Neoplasias, Humanos, medicine.anatomical_structure, Neoplasias de la mama, Chemicals and Drugs::Biomedical and Dental Materials::Dental Materials::Dental Implants [Medical Subject Headings], UNESCO::CIENCIAS MÉDICAS, Maxillectomy, Diseases::Stomatognathic Diseases::Mouth Diseases::Peri-Implantitis [Medical Subject Headings], Oral Surgery, Resorción ósea, medicine.drug, medicine.medical_specialty, Odontología, Diseases::Musculoskeletal Diseases::Bone Diseases::Osteonecrosis [Medical Subject Headings], Bone resorption, Breast cancer, Osteoclast, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::Imidazoles [Medical Subject Headings], medicine, Periimplantitis, General Dentistry, Zoledronic acid, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Osteonecrosis of the jaw, business.industry, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Bone Remodeling::Bone Resorption [Medical Subject Headings], Osteoclastos, medicine.disease, Surgery, Check Tags::Female [Medical Subject Headings], business
Abstract

Journal Article; Bisphosphonates (BP) are a type of drug known to inhibit bone resorption through complex interventions. Their primary mechanism of action is aimed at the cellular level, inhibiting osteoclast activity and so bone resorption. BPs are widely used, with many patients receiving continuous treatment for years. But it is well known that these drugs can produce osteonecrosis of the jaw (ONJ). Zoledronic acid (ZA) is an intravenous BP used in the treatment and prophylaxis of bone disease in patients with malignant tumors with bone implication. ZA is the most potent BP in clinical development. This report describes the case of a 62-year-old woman with breast cancer antecedents which relapsed, who had received a maxillary dental implant two years before the start of therapy with zoledronic acid. She later developed osteonecrosis of the jaw (ONJ), which began in the peri-implant area, and was treated for stage 3 ONJ by sub-total maxillectomy. Key words:Bisphosphonates, zoledronic acid, osteonecrosis of the jaw, peri-implantitis, maxillectomy. Yes

Published
2015
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29. Randomized Phase 3 Trial of Fluorouracil, Epirubicin, and Cyclophosphamide Alone or Followed by Paclitaxel for Early Breast Cancer

Author

Miguel, Martín, Alvaro, Rodríguez-Lescure, Amparo, Ruiz, Emilio, Alba, Lourdes, Calvo, Manuel, Ruiz-Borrego, Blanca, Munárriz, César A, Rodríguez, Carmen, Crespo, Enrique, de Alava, José Antonio, López García-Asenjo, María Dolores, Guitián, Sergio, Almenar, Jesús Fernando, González-Palacios, Francisco, Vera, José, Palacios, Manuel, Ramos, Jose Manuel, Gracia Marco, Ana, Lluch, Isabel, Alvarez, Miguel Angel, Seguí, José Ignacio, Mayordomo, Antonio, Antón, José Manuel, Baena, Arrate, Plazaola, Alfonso, Modolell, Amadeu, Pelegrí, Jose Ramón, Mel, Enrique, Aranda, Encarna, Adrover, José Valero, Alvarez, José Luis, García Puche, Pedro, Sánchez-Rovira, Sonia, Gonzalez, José Manuel, López-Vega, M Francisca, Garijo, GEICAM 9906 Study Investigators, [Martín,M] Department of Medical Oncology, Hospital Universitario San Carlos, Madrid, Spain. [López García-Asenjo,JA] Department of Pathology, Hospital Universitario San Carlos, Madrid, Spain. [Rodríguez-Lescure,A] Department of Medical Oncology, Hospital Universitario de Elche, Spain. [Ruiz,A] Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain. [Almenar,S] Department of Pathology, Instituto Valenciano de Oncologia, Valencia, Spain. [Alba Conejo,E] Department of Medical Oncology, Hospital Virgen de la Victoria, Málaga, Spain. [Calvo,L] Department of Medical Oncology, Complejo Hospitalario Juan Canalejo, La Coruña, Spain. [Guitián,MD] Department of Pathology, Complejo Hospitalario Juan Canalejo, La Coruña, Spain. [Ruiz-Borrego,M] Department of Medical Oncology, Hospital Vírgen del Rocío, Sevilla, Spain [Palacios,J] Department of Pathology, Hospital Vírgen del Rocío, Sevilla, Spain. [Muñárriz,B] Department of Medical Oncology, Hospital La Fe, Valencia, Spain. [Vera,F] Department of Pathology, Hospital La Fe, Valencia, Spain. [Rodríguez, CA] Department of Medical Oncology, Hospital Universitario de Salamanca, Salamanca, Spain. [Crespo,C] Department of Medical Oncology, Hospital Ramón y Cajal, Madrid, Spain. [González-Palacios,JF] Department of Pathology, Hospital Ramón y Cajal, Madrid, Spain. [de Álava,E] Department of Pathology, Centro de Investigación del Cáncer, Salamanca, Spain. [Ramos,M] Department of Medical Oncology, Centro Oncológico de Galicia, La Coruña, Spain. [Gracia Marco,JM] Department of Medical Oncology, Hospital de Cabueñes, Gijón, Spain. [Lluch,A] Department of Medical Oncology, Hospital Clínico Universitario de Valencia, Valencia, Spain. [Álvarez,I] Department of Medical Oncology, Hospital de Donostia, San Sebastián, Spain. [Seguí,MA] Department of Medical Oncology, Hospital Parc Taulí, Sabadell, Spain. [Mayordomo,JI] Department of Medical Oncology, Hospital Clínico Lozano Blesa, Zaragoza, Spain. [Antón,A] Department of Medical Oncology, Hospital Miguel Servet, Zaragoza, Spain. [Baena,JM] Department of Medical Oncology, Complejo Hospitalario Puerta del Mar, Cádiz, Spain. [Plazaola,A] Department of Medical Oncology, Instituto Oncológico de Guipúzcoa, San Sebastián, Spain. [Modolell,A] Department of Medical Oncology, Clínica Corachan, Barcelona, Spain. [Pelegrí,A] Department of Medical Oncology, Hospital Universitario San Joan de Reus, Tarragona, Spain. [Mel,JR] Department of Medical Oncology, Complejo Hospitalario Xeral Calde, Lugo, Spain. [Aranda,E] Department of Medical Oncology, Hospital Provincial de Córdoba, Córdoba, Spain. [Adrover,E] Department of Medical Oncology, Hospital General de Alicante, Alicante, Spain. [Valero Álvarez,J] Hospital Provincial de Zamora, Spain. [García Puche,JL] Department of Medical Oncology, Hospital San Cecilio de Granada, Granada, Spain. [Sánchez-Rovira,P] Department of Medical Oncology, Hospital Ciudad de Jaén, Jaén, Spain. [González,S] Department of Medical Oncology, Mutua de Terrasa, Terrasa, Spain. [López-Vega,JM] Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Spain., and Department of Medical Oncology, Hospital Ciudad de Jaén, Jaén, Spain

Subjects
Oncology, medicine.medical_treatment, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Supervivencia sin Enfermedad, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, erbB-2 [Medical Subject Headings], Antineoplastic Combined Chemotherapy Protocols, Estimación de Kaplan-Meier, Receptor erbB-2, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy Protocols [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration Schedule [Medical Subject Headings], Hazard ratio, Pronóstico, Epirrubicina, Prognosis, Immunohistochemistry, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Carcinoma, Ductal::Carcinoma, Ductal, Breast [Medical Subject Headings], Receptors, Estrogen, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Neoplasm Staging [Medical Subject Headings], Chemicals and Drugs::Biological Factors::Biological Markers::Tumor Markers, Biological [Medical Subject Headings], Receptors, Progesterone, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Alicyclic::Cycloparaffins::Cyclodecanes::Taxoids::Paclitaxel [Medical Subject Headings], medicine.medical_specialty, Paclitaxel, Fluorouracilo, Axillary lymph nodes, Resultado del Tratamiento, Anciano, Disease-Free Survival, Drug Administration Schedule, Breast cancer, Carcinoma Lobular, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Adjuvant therapy, Humans, Cyclophosphamide, Aged, ERBB2 protein, human, medicine.disease, Carcinoma, Lobular, Check Tags::Female [Medical Subject Headings], Modelos de Riesgos Proporcionales, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Histocytological Preparation Techniques::Staining and Labeling::In Situ Hybridization::In Situ Hybridization, Fluorescence [Medical Subject Headings], Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Survival Analysis::Disease-Free Survival [Medical Subject Headings], Cancer Research, Receptor, ErbB-2, Kaplan-Meier Estimate, Antineoplásicos Fitogénicos, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Carcinoma, Lobular [Medical Subject Headings], Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidinones::Uracil::Fluorouracil [Medical Subject Headings], Infusions, Intravenous, In Situ Hybridization, Fluorescence, Carcinoma, Ductal, Breast, Neoplasias de la Mama, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [Medical Subject Headings], Middle Aged, Chemotherapy regimen, Treatment Outcome, medicine.anatomical_structure, Female, Fluorouracil, Breast disease, Infusiones Intravenosas, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents::Antineoplastic Agents, Phytogenic [Medical Subject Headings], Epirubicin, medicine.drug, Adult, Protocolos de Quimioterapia Combinada Antineoplásica, Hibridación Fluorescente In Situ, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Halogenated::Mustard Compounds::Nitrogen Mustard Compounds::Phosphoramide Mustards::Cyclophosphamide [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone [Medical Subject Headings], Breast Neoplasms, Ciclofosfamida, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Statistical::Proportional Hazards Models [Medical Subject Headings], Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Immunochemistry [Medical Subject Headings], Predictive Value of Tests, Internal medicine, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Polycyclic Hydrocarbons, Aromatic::Naphthacenes::Anthracyclines::Daunorubicin::Doxorubicin::Epirubicin [Medical Subject Headings], Biomarkers, Tumor, medicine, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Neoplasm Staging, Proportional Hazards Models, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings], Receptores de Progesterona, Chemotherapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis::Kaplan-Meier Estimate [Medical Subject Headings], business.industry, Esquema de Medicación, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration Routes::Infusions, Parenteral::Infusions, Intravenous [Medical Subject Headings], Antineoplastic Agents, Phytogenic, Estadificación de Neoplasias, Receptores Estrogénicos, Surgery, Marcadores Biológicos de Tumor, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], business, Carcinoma Ductal de Mama, Inmunohistoquímica
Abstract

Clinical Trial, Phase III; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; BACKGROUND Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting. METHODS After breast cancer surgery, women with lymph node-positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study-5-year disease-free survival (DFS)-was assessed by Kaplan-Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided. RESULTS Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval [CI] = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio [HR] = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) (P = .017), number of involved axillary lymph nodes (P < .001), tumor size (P = .020), hormone receptor status (P = .004), and HER2 status (P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment. CONCLUSIONS Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy. Yes

Published
2008
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30. Integral strategy to supportive care in breast cancer survivors through occupational therapy and a m-health system: design of a randomized clinical trial

Author

Manuel Arroyo-Morales, Francisco Álvarez-Salvago, Irene Cantarero-Villanueva, Noelia Galiano-Castillo, Lydia Martín-Martín, Carolina Fernández-Lao, Mario Lozano-Lozano, Carmen Sánchez-Salado, [Lozano-Lozano, Mario] Univ Granada, Dept Phys Therapy, Granada, Spain, [Martin-Martin, Lydia] Univ Granada, Dept Phys Therapy, Granada, Spain, [Galiano-Castillo, Noelia] Univ Granada, Dept Phys Therapy, Granada, Spain, [Alvarez-Salvago, Francisco] Univ Granada, Dept Phys Therapy, Granada, Spain, [Cantarero-Villanueva, Irene] Univ Granada, Dept Phys Therapy, Granada, Spain, [Fernandez-Lao, Carolina] Univ Granada, Dept Phys Therapy, Granada, Spain, [Arroyo-Morales, Manuel] Univ Granada, Dept Phys Therapy, Granada, Spain, [Lozano-Lozano, Mario] Mixed Univ Sport & Hlth Inst iMUDS, Granada, Spain, [Cantarero-Villanueva, Irene] Mixed Univ Sport & Hlth Inst iMUDS, Granada, Spain, [Fernandez-Lao, Carolina] Mixed Univ Sport & Hlth Inst iMUDS, Granada, Spain, [Arroyo-Morales, Manuel] Mixed Univ Sport & Hlth Inst iMUDS, Granada, Spain, [Galiano-Castillo, Noelia] Univ Granada, Inst Biomed Res Ibs GRANADA, Univ Hosp Complex Granada, Granada, Spain, [Cantarero-Villanueva, Irene] Univ Granada, Inst Biomed Res Ibs GRANADA, Univ Hosp Complex Granada, Granada, Spain, [Fernandez-Lao, Carolina] Univ Granada, Inst Biomed Res Ibs GRANADA, Univ Hosp Complex Granada, Granada, Spain, [Arroyo-Morales, Manuel] Univ Granada, Inst Biomed Res Ibs GRANADA, Univ Hosp Complex Granada, Granada, Spain, [Sanchez-Salado, Carmen] Virgen de las Nieves Hosp, Breast Oncol Unit, Granada, Spain, Spanish Ministry of Economy and Competitiveness (Plan Estatal de I + D + I), Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III, Fondos Estructurales de la Union Europea (FEDER), Spanish Ministry of Education, [Lozano-Lozano,M, Martín-Martín,L, Galiano-Castillo,B, Álvarez-Salvago,F, Cantarero-Villanueva,I, Fernández-Lao,C, Arroyo-Morales,M] Department Physical Therapy, University of Granada, Granada, Spain. [Lozano-Lozano,M, Arroyo-Morales,M] Mixed University Sport and Health Institute (iMUDS), Granada, Spain. [Galiano-Castillo,N, Arroyo-Morales,M] Institute for Biomedical Research ibs.GRANADA, University Hospital Complex of Granada/ University of Granada,Granada, Spain. [Sánchez-Salado,C] Breast Oncology Unit, Virgen de las Nieves Hospital, Granada, Spain., and The study was funded by the Spanish Ministry of Economy and Competitiveness (Plan Estatal de I + D + I 2013-2016), Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI14/01627), Fondos Estructurales de la Unión Europea (FEDER) and by the Spanish Ministry of Education (FPU14/01069).

Subjects
medicine.medical_treatment, Physical fitness, Hospital Anxiety and Depression Scale, Anatomy::Body Regions::Breast [Medical Subject Headings], law.invention, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Study Protocol, 0302 clinical medicine, Mobile applications, Randomized controlled trial, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Muscle Strength::Hand Strength [Medical Subject Headings], law, Depresión, Neoplasms, 030212 general & internal medicine, Survivors, Breast, Phenomena and Processes::Metabolic Phenomena::Body Composition [Medical Subject Headings], Rehabilitation, Health Policy, Mama, Ingestión de energía, Femenino, Middle Aged, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet::Energy Intake [Medical Subject Headings], Telemedicine, Humanos, Computer Science Applications, 030220 oncology & carcinogenesis, Neoplasias de la mama, Body-composition, Arm, Brazo, Anxiety, Female, medicine.symptom, Fuerza de la mano, Anatomy::Body Regions::Extremities::Upper Extremity::Arm [Medical Subject Headings], Occupational therapy, Adult, Quality of life, medicine.medical_specialty, Health Informatics, Intervention, Breast Neoplasms, Validity, Ansiedad, 03 medical and health sciences, Breast cancer, medicine, Adjuvant therapy, Humans, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Emotions::Anxiety [Medical Subject Headings], Composición corporal, Exercise, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Cognición, Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Cognition [Medical Subject Headings], Curative treatment, business.industry, medicine.disease, Check Tags::Female [Medical Subject Headings], Physical therapy, Physical-activity, Surgery, Quality-of-life, European-organization, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Behavioral Symptoms::Depression [Medical Subject Headings], business
Abstract

Background: Technological support using e-health mobile applications (m-health) is a promising strategy to improve the adherence to healthy lifestyles in breast cancer survivors (excess in energy intake or low physical activity are determinants of the risk of recurrence, second cancers and cancer mortality). Moreover, cancer rehabilitation programs supervised by health professionals are needed due to the inherent characteristics of these breast cancer patients. Our main objective is to compare the clinical efficacy of a m-health lifestyle intervention system alone versus an integral strategy to improve Quality of Life in breast cancer survivors. Methods: This therapeutic superiority study will use a two-arm, assessor blinded parallel RCT design. Women will be eligible if: they are diagnosed of stage I, II or III-A breast cancer; are between 25 and 75 years old; have a Body Mass Index > 25 kg/m2; they have basic ability to use mobile apps; they had completed adjuvant therapy except for hormone therapy; and they have some functional shoulder limitations. Participants will be randomized to one of the following groups: integral group will use a mobile application (BENECA APP) and will receive a face-to-face rehabilitation (8-weeks); m-health group will use the BENECA app for 2-months and will received usual care information. Study endpoints will be assessed after 8 weeks and 6 months. The primary outcome will be Quality of Life measured by The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core and breast module. The secondary outcomes: body composition; upper-body functionality (handgrip, Disability of the Arm, Shoulder and Hand questionnaire, goniometry); cognitive function (Wechsler Adult Intelligence Scale, Trail Making Test); anxiety and depression (Hospital Anxiety and Depression Scale); physical fitness (Short version of the Minnesota Leisure Time Physical Activity Questionnaire, Self-Efficacy Scale for Physical Activity); accelerometry and lymphedema. Discussion: This study has been designed to seek to address the new needs for support and treatment of breast cancer survivors, reflecting the emerging need to merge new low cost treatment options with much-needed involvement of health professionals in this type of patients. Trial registration: ClinicalTrials.gov Identifier: NCT02817724 (date of registration: 22/06/2016)., The study was funded by the Spanish Ministry of Economy and Competitiveness (Plan Estatal de I + D + I 2013-2016), Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI14/01627), Fondos Estructurales de la Unión Europea (FEDER) and by the Spanish Ministry of Education (FPU14/01069). This is part of a Ph.D. Thesis conducted in the Clinical Medicine and Public Health Doctoral Studies of the University of Granada, Spain.

Published
2016

31. Circulating prolactin and in situ breast cancer risk in the European EPIC cohort: a case-control study

Author

Sabina Rinaldi, Aurelio Barricarte, Dimitrios Trichopoulos, Evelyn M. Monninkhof, Françoise Clavel-Chapelon, Anne Tjønneland, Amalia Mattiello, Laure Dossus, Renée T. Fortner, Virginia Menéndez, Vittorio Krogh, Kim Overvad, Fulvio Ricceri, Antonia Trichopoulou, Rosario Tumino, Laura Baglietto, Kaja Tikk, Elisabete Weiderpass, Disorn Sookthai, Ruth C. Travis, Timothy J. Key, María José Sánchez, Antonio Agudo, Giovanna Masala, Isabelle Romieu, Elio Riboli, Heiner Boeing, María Dolores Chirlaque, Malin Sund, Theron Johnson, Anja Olsen, N. Charlotte Onland-Moret, Anne Andresson, Rudolf Kaaks, Hbas Bueno-de-Mesquita, Pagona Lagiou, Pilar Amiano, Kay-Tee Khaw, Melissa A. Merritt, [Tikk,K, Sookthai,D, Fortner,RT, Johnson,T, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Rinaldi,S, Romieu,I] Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France. [Tjønneland,D, Olsen,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Clavel-Chapelon,F, Dossus,l] INSERM, Centre for Research in Epidemiology and Population Health [CESP], Nutrition, Hormones and Women’s Health team, Villejuif, France. [Clavel-Chapelon,F, Dossus,l] Univ Paris Sud, Villejuif, France. [Clavel-Chapelon,F, Dossus,l] IGR, Villejuif, France. [Baglietto,L] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Melbourne, Australia. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, Germany. [Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece.[Trichopoulou,A, Lagiou.P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Goudi, Athens, Greece. [Trichopoulou,A, Lagiou,P, Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, Florence, Italy. [Krogh,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.P.Arezzo' Hospital ASP, Ricceri, Ragusa, Italy. [Ricceri,F] Unit of Cancer Epidemiology, AO Citta’ della Salute e della Scienza, University of Turin, Torino, Italy. Unit of Cancer Epidemiology, AO Citta’ della Salute e della Scienza, University of Turin, Torino, Italy. [Mattiello,A] Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. [Agudo,A] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology-ICO, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Menéndez,V] Public Health Directorate, Asturias, Spain. [Sánchez,M] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitario de Granada (Granada.ibs), Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Reserach Institute, San Sebastian, Spain. [Chirlaque,M] Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Sánchez, M, Amiano, P, Chirlaque,M, Barricarte,A] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER de Epidemiología y Salud Pública (CIBERESP)), Madrid, Spain. [Bueno-de-Mesquita,H] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Bueno-de-Mesquita,H, Merritt,MA, Riboli,E] Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College, London, UK. [Monninkhof,EM, Onland-Moret,NC] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Andresson,A] Department of Radiation Sciences, University of Umeå, Umeå, Sweden. [Sund,M] Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland, [Khaw,K] School of Clinical Medicine, University of Cambridge, Cambridge, UK. [Key,TJ, and Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Tikk,K] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.

Subjects
Oncology, Cancer Research, Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Gonadotropins::Gonadotropins, Pituitary::Prolactin [Medical Subject Headings], PERIOD, Prolactina, Cohort Studies, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Breast cancer, Risk Factors, REPRODUCIBILITY, HISTORY, Odds Ratio, 0303 health sciences, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Neoplasias de la Mama, Estudios de Casos y Controles, Middle Aged, Adult, Aged, Breast Neoplasms, Carcinoma in Situ, Case-Control Studies, Europe, Female, Follow-Up Studies, Humans, Logistic Models, Menopause, Prolactin, 3. Good health, European Prospective Investigation into Cancer and Nutrition, POSTMENOPAUSAL WOMEN, PREMENOPAUSAL WOMEN, 030220 oncology & carcinogenesis, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk [Medical Subject Headings], Cohort, Life Sciences & Biomedicine, Cohort study, Research Article, medicine.medical_specialty, CARCINOMA, STEROID-HORMONES, Riesgo, Càncer de mama, 03 medical and health sciences, Internal medicine, parasitic diseases, medicine, Journal Article, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], 030304 developmental biology, Cancer och onkologi, Science & Technology, business.industry, Carcinoma in situ, Case-control study, Odds ratio, medicine.disease, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma in Situ [Medical Subject Headings], Cancer and Oncology, PLASMA PROLACTIN, business
Abstract

Introduction The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention. Methods We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects. Results We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2 = 1.35 (95% CI 1.04-1.76), P-trend = 0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (P-het = 0.98) or baseline HT use (P-het = 0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (P-trend = 0.06 vs P-trend = 0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors = 4 years after blood donation (P-trend = 0.01 vs P-trend = 0.63; P-het = 0.04) and among nulliparous women compared to parous women (P-trend = 0.03 vs P-trend = 0.15; P-het = 0.07). Conclusions Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention.

Published
2015
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32. A microRNA Signature Associated with Early Recurrence in Breast Cancer

Author

Alfonso Pérez Sánchez, Emilio Alba, José Manuel Lozano, Luis G. Perez-Rivas, Bella Pajares, Luis Vicioso, Vanessa de Luque, Nuria Ribelles, Rosario Carmona, Enrique Viguera, José M. Jerez, M. Gonzalo Claros, [Pérez-Rivas,LG, Luque,V de, Pajares,B, Sánchez,A, Ribelles,N, Alba,E, Lozano,J] Laboratorio de Oncología Molecular, Servicio de Oncología Médica, Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Jerez, JM] Departamento de Lenguajes y Ciencias de la Computación, Universidad de Málaga, Spain. [Carmona, R, Claros, MG] Plataforma Andaluza de Bioinformática, Universidad de Málaga, Spain. [Vicioso, L] Servicio de Anatomía Patológica, Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Claros, MG, Lozano, J] Departmento de Biología Molecular y Bioquímica, Universidad de Málaga, Spain. [Viguera, E] Departmento of Biología Celular, Genética y Fisiología Animal, Universidad de Málaga, Spain., and This work was supported by a grant from the Spanish Society of Medical Oncology (SEOM, to NR) and by grants from the Spanish Ministerio de Economía, (SAF2010-20203 to J.L and TIN2010-16556 to J.J) and from the Junta de Andalucía (TIN-4026, to JJ).

Subjects
Time Factors, Microarray, Microarrays, medicine.medical_treatment, lcsh:Medicine, Bioinformatics, Biochemistry, Metastasis, Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Movement [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], RNA interference, Surgical oncology, Nucleic Acids, Molecular Cell Biology, Basic Cancer Research, Breast Tumors, Medicine and Health Sciences, Cluster Analysis, lcsh:Science, Oligonucleotide Array Sequence Analysis, MicroARNs, Multidisciplinary, Pronóstico, Neoplasias de la Mama, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Targeting [Medical Subject Headings], Genomics, Middle Aged, Primary tumor, Interferencia de ARN, Bioassays and Physiological Analysis, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Sensitivity and Specificity::Predictive Value of Tests [Medical Subject Headings], Oncology, Epigenetics, Female, Transcriptome Analysis, Cancer Screening, Research Article, Breast surgery, Breast Neoplasms, Biology, Research and Analysis Methods, Disease-Free Survival, Breast cancer, Diseases::Neoplasms::Neoplastic Processes::Neoplasm Metastasis [Medical Subject Headings], medicine, Genetics, Cancer Detection and Diagnosis, Biomarkers, Tumor, Marcación de Gen, Humans, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Biology and life sciences, Valor Predictivo de las Pruebas, Microarray analysis techniques, Gene Expression Profiling, lcsh:R, Metástasis de la Neoplasia, Computational Biology, Cancers and Neoplasms, Cell Biology, medicine.disease, Genome Analysis, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Neoplastic [Medical Subject Headings], Gene expression profiling, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [Medical Subject Headings], MicroRNAs, Gene Ontology, Movimiento Celular, ROC Curve, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic::Gene Silencing::RNA Interference [Medical Subject Headings], Procedimientos Quirúrgicos Operativos, RNA, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], lcsh:Q, Neoplasm Recurrence, Local, Genome Expression Analysis, Regulación Neoplásica de la Expresión Génica
Abstract

Journal Article; Recurrent breast cancer occurring after the initial treatment is associated with poor outcome. A bimodal relapse pattern after surgery for primary tumor has been described with peaks of early and late recurrence occurring at about 2 and 5 years, respectively. Although several clinical and pathological features have been used to discriminate between low- and high-risk patients, the identification of molecular biomarkers with prognostic value remains an unmet need in the current management of breast cancer. Using microarray-based technology, we have performed a microRNA expression analysis in 71 primary breast tumors from patients that either remained disease-free at 5 years post-surgery (group A) or developed early (group B) or late (group C) recurrence. Unsupervised hierarchical clustering of microRNA expression data segregated tumors in two groups, mainly corresponding to patients with early recurrence and those with no recurrence. Microarray data analysis and RT-qPCR validation led to the identification of a set of 5 microRNAs (the 5-miRNA signature) differentially expressed between these two groups: miR-149, miR-10a, miR-20b, miR-30a-3p and miR-342-5p. All five microRNAs were down-regulated in tumors from patients with early recurrence. We show here that the 5-miRNA signature defines a high-risk group of patients with shorter relapse-free survival and has predictive value to discriminate non-relapsing versus early-relapsing patients (AUC = 0.993, p-value

Published
2014

33. Predicting response and survival in chemotherapy-treated triple-negative breast cancer

Author

Lourdes Calvo, Brandy Pitcher, Chun-Yang Fan, Álvaro Rodríguez-Lescure, Lisa A. Carey, Blanca Munárriz, William T. Barry, Eric P. Winer, Eva Carrasco, Marc L. Citron, Aleix Prat, Nuria Ribelles, Maggie C.U. Cheang, Elaine R. Mardis, MC Liu, Manuel Ruiz-Borrego, Jose Ignacio Chacon, A. Arcusa, Rafael Caballero, Joan Albanell, E. Alba, Tammi L. Vickery, Matthew J. Ellis, Joel S. Parker, A. Lluch, Clifford A. Hudis, Yufeng Li, Miguel Angel Seguí-Palmer, Ángel L Guerrero, Barbara Adamo, Arrate Plazaola, Margaret L. Gulley, Miguel Martin, Octavio Burgues, José A. López, Maria Vidal, Zhiyuan Hu, Charles M. Perou, Universitat de Barcelona, [Prat,A, Adamo,B, Vidal,M.J] Translational Genomics Group, Vall D'Hebron Institute of Oncology (VHIO) Barcelona, Spain. [Prat,A] Department of Medicine, Universitat Autònoma de Barcelona, Spain. [Lluch,A, Burgues,O] Department of Medical Oncology, Department of Pathology, Hospital Clínico Universitario de Valencia, Spain. [Albanell,J] Department of Medical Oncology, Hospital Del Mar, IMIM, Barcelona, Spain. [Albanell,J] Department of Medical Oncology, Universitat Pompeu Fabra (UPF), Barcelona, Spain. [Barry,W.T] Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, United States. [Fan,C, Parker,J.S, Cheang,M.C.U, Li,Y, Hu,Z, Gulley,M.L, Carey,L.A, Perou,C.M] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States. [Chacón,J.I] Department of Medical Oncology, Hospital Virgen de la Salud, Toledo, Spain. [Parker,J.S, Perou,C.M] Department of Genetics, University of North Carolina, Chapel Hill, NC, United States. [Calvo,L] Department of Medical Oncology, Complexo Hospitalario Universitario de A Coruña, A Coruña, Spain. [Plazaola,A] Department of Medical Oncology, Onkologikoa, San-Sebastián, Spain. [Arcusa,A] Department of Medical Oncology, Consorci Sanitari de Terrassa, Barcelona, Spain. [Seguí-Palmer,M.A] Department of Medical Oncology, Corporació Sanitària Parc Taulí, Sabadell, Spain. [Ribelles,N, Alba,E] Department of Medical Oncology, Department of Pathology, Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Rodríguez-Lescure,A] Department of Medical Oncology, Hospital General de Elche, Alicante, Spain. [Guerrero,A] Department of Medical Oncology, Instituto Valenciano de Oncología (IVO), Valencia, Spain. [Ruiz-Borrego,M] Department of Medical Oncology, Hospital Universitario Virgen Del Rocío, Sevilla, Spain. [Munarriz,B] Department of Medical Oncology, Hospital Universitario la Fe, Valencia, Spain. [López,J.A] Department of Medical Oncology, Hospital San Camilo, Madrid, Spain.[Pitcher,B.N] Alliance Statistical and Data Center, Duke University, Durham, NC, United States. [Liu,M.C] Department of Oncology, Mayo Clinic, Rochester, MN, United States. [Citron,M.L] ProHEALTH Care Assoc., LLP, Lake Success, NY, United States. [Ellis,M.J, Mardis,E, Vickery,T] Department of Oncology, Washington University St. Louis, MO, United States. [Hudis,C.A] Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States. [Winer,E.P] Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States. [Caballero,R, Carrasco,E, Martín,M] GEICAM (Spanish Breast Cancer Research Group), Madrid, Spain. [Martín,M] Department of Medical Oncology, Instituto de Investigación Sanitaria, Hospital Universitario Gregorio Marañón, Madrid, Spain. [Perou,C.M] Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, United States., and This work was supported by funds from the NCI Breast SPORE program Grant No. P50-CA58223-09A1 (CMP), by RO1-CA138255 (CMP), by the Breast Cancer Research Foundation (CMP and MJE), National Cancer Institute (NCI) Strategic Partnering to Evaluate Cancer Signatures Grant No. U01 CA114722-01 (MJE), by the Sociedad Española de Oncología Médica (AP), by FEDER (RETICC-RD12/0036/0051, RD12/0036/0042, RD12/0036/0076, RD12/0036/0070), by Instituto de Salud Carlos III—PI13/01718 (AP), by Banco Bilbao Vizcaya Argentaria (BBVA) Foundation (AP) and by the Alliance Statistics and Data Center (U10-CA33601).

Subjects
Oncology, Cancer Research, Análisis de supervivencia, Colorectal cancer, Triple Negative Breast Neoplasms, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], chemotherapy, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Prostate cancer, 0302 clinical medicine, Clinical trials, Breast cancer, Quimioteràpia, Triple-negative breast cancer, Subtypes, 0303 health sciences, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Survival Analysis [Medical Subject Headings], subtypes, Genomics, Middle Aged, 3. Good health, Treatment Outcome, Estudi de casos, 030220 oncology & carcinogenesis, Female, Neoadjuvant, Basal like, intrinsic, medicine.medical_specialty, Antineoplastic Agents, basal like, Càncer de mama, 03 medical and health sciences, breast cancer, Internal medicine, genomics, medicine, Humans, Chemotherapy, Lung cancer, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Survival analysis, 030304 developmental biology, Proportional hazards model, business.industry, neoadjuvant, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [Medical Subject Headings], Neoplasias de la mama triple negativas, Antineoplásicos, medicine.disease, Survival Analysis, Expressió gènica, Intrisic, Check Tags::Female [Medical Subject Headings], Intrinsic, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Clinical Study, Gene expression, Case studies, Resultado del tratamiento, Health Care::Health Services Administration::Quality of Health Care::Outcome and Process Assessment (Health Care)::Outcome Assessment (Health Care)::Treatment Outcome [Medical Subject Headings], Skin cancer, business, Assaigs clínics
Abstract

This work was presented, in part, as an oral communication at the ASCO 2012 annual meeting (Abstract #10500). Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; BACKGROUND In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC). METHODS Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated. RESULTS Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival. CONCLUSIONS The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not. Yes

Published
2014

34. ESR1 gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients

Author

Salomón Menjón, José Mariano Ruiz de Almodóvar, Joaquina Martínez-Galán, Rosario Del Moral, J.J. López-Peñalver, B. Torres-Torres, Juan Ramón Delgado, S. Ríos, Clara Chamorro, Ángel Concha, María Isabel Núñez, [Martínez-Galán,J, Delgado, JR] Department of Medical Oncology, Hospital Universitario Virgen de las Nieves, University of Granada. Granada, Spain. [Torres-Torres,B, López-Peñalver,J, Ruiz De Almodóvar,JM] Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain. [Núñez,MA, Ríos,S] Departamento de Radiología y Medicina Física, Facultad de Medicina de Granada, Granada, Spain. [Del Moral,R] Servicio de Oncología Radioterápica, Hospital Universitario Virgen de las Nieves, Granada, Spain. [Menjón,S] ervicio de Ginecología, Hospital Universitario Virgen de las Nieves, Granada, Spain. [Concha,A, Chamorro,C] Servicio de Anatomía Patológica, Hospital Universitario Virgen de las Nieves, Granada, Spain., and The study was funded, in part, by a grant from the Ministerio de Educación y Ciencia (CICYT: SAF 2004–00889).

Subjects
Cancer Research, Bisulfite sequencing, Estrogen receptor, Triple Negative Breast Neoplasms, Polymerase Chain Reaction, Breast cancer, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents::Antineoplastic Agents, Hormonal [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Methylation [Medical Subject Headings], Promoter Regions, Genetic, Aged, 80 and over, Antineoplásicos Hormonales, Neoplasias de la Mama, Femenino, Methylation, Middle Aged, Prognosis, Immunohistochemistry, Gene Expression Regulation, Neoplastic, Phenotype, Oncology, Metilación, DNA methylation, Luminal phenotypes, Female, Metilación de ADN, Research Article, Adult, Epigénesis Genética, Breast Neoplasms, Biology, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [Medical Subject Headings], Genetics, medicine, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, Gene Silencing, Estrogen receptor beta, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic [Medical Subject Headings], Estrogen Receptor alpha, DNA Methylation, medicine.disease, Receptores Estrogénicos, Check Tags::Female [Medical Subject Headings], Cancer research, CpG Islands, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Alkylation::Methylation [Medical Subject Headings], Estrogen receptor alpha
Abstract

[Background] Tumor expression of estrogen receptor (ER) is an important marker of prognosis, and is predictive of response to endocrine therapy in breast cancer. Several studies have observed that epigenetic events, such methylation of cytosines and deacetylation of histones, are involved in the complex mechanisms that regulate promoter transcription. However, the exact interplay of these factors in transcription activity is not well understood. In this study, we explored the relationship between ER expression status in tumor tissue samples and the methylation of the 5′ CpG promoter region of the estrogen receptor gene (ESR1) isolated from free circulating DNA (fcDNA) in plasma samples from breast cancer patients. [Methods] Patients (n = 110) with non-metastatic breast cancer had analyses performed of ER expression (luminal phenotype in tumor tissue, by immunohistochemistry method), and the ESR1-DNA methylation status (fcDNA in plasma, by quantitative methylation specific PCR technique). [Results] Our results showed a significant association between presence of methylated ESR1 in patients with breast cancer and ER negative status in the tumor tissue (p = 0.0179). There was a trend towards a higher probability of ESR1-methylation in those phenotypes with poor prognosis i.e. 80% of triple negative patients, 60% of HER2 patients, compared to 28% and 5.9% of patients with better prognosis such as luminal A and luminal B, respectively. [Conclusion] Silencing, by methylation, of the promoter region of the ESR1 affects the expression of the estrogen receptor protein in tumors of breast cancer patients; high methylation of ESR1-DNA is associated with estrogen receptor negative status which, in turn, may be implicated in the patient’s resistance to hormonal treatment in breast cancer. As such, epigenetic markers in plasma may be of interest as new targets for anticancer therapy, especially with respect to endocrine treatment., The study was funded, in part, by a grant from the Ministerio de Educación y Ciencia (CICYT: SAF 2004–00889).

Published
2014

35. Pattern of recurrence of early breast cancer is different according to intrinsic subtype and proliferation index

Author

Begoña Jiménez, Luis Vicioso, Elena Gallego, Bella Pajares, Antonia Márquez, Emilio Alba, L. Perez-Villa, Alfonso Sánchez-Muñoz, Martina Alvarez, Leonardo Franco, José M. Jerez, Vanessa de Luque, Nuria Ribelles, Luis G. Perez-Rivas, [Ribelles, N, Pajares, B, Jiménez, B, Luque, V de, Márquez, A, Sánchez-Muñoz, A, Pérez-Rivas, L, Alba, E] Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Pérez-Villa, L, Vicioso, L, Gallego, E] Department of Pathology, Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Jerez, JM, Franco, L] Department of Languages and Computer Science, University of Málaga, Spain. [Álvarez, M] Department of Pathology, University of Malaga, Spain., and This work was supported by Grant-in Aid PI081797 from the Ministry of Science and Innovation of Spain (Fondo de Investigaciones Sanitarias). The authors acknowledge funding through grants TIN2010-16556 (MICINN-Spain), TIC-4026/2008 (Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía) and PI-0310/2008 (Consejería de Salud. Junta de Andalucía), all of which include European Regional Development Fund support.

Subjects
Oncology, Proliferation index, Databases, Factual, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Combined Modality Therapy::Chemotherapy, Adjuvant [Medical Subject Headings], Diseases::Neoplasms::Neoplasms, Hormone-Dependent [Medical Subject Headings], Estrogen receptor, Factor de Crecimiento Epidérmico, Antígeno Ki-67, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Surgical oncology, Risk Factors, Neoplasias Hormono-Dependientes, Epidermal growth factor receptor, Neoplasm Metastasis, skin and connective tissue diseases, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone [Medical Subject Headings], Medicine(all), biology, Queratina-5, Neoplasias de la Mama, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [Medical Subject Headings], Middle Aged, Queratina-6, Immunohistochemistry, Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::Keratins::Keratins, Type II::Keratin-5 [Medical Subject Headings], Female, Research Article, Adult, medicine.medical_specialty, Breast Neoplasms, Cytokeratin, Young Adult, Breast cancer, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, Epidermal Growth Factor [Medical Subject Headings], Internal medicine, Progesterone receptor, medicine, Biomarkers, Tumor, Humans, Mastectomía, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Cell Proliferation, Neoplasm Staging, Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::Keratins::Keratins, Type II::Keratin-6 [Medical Subject Headings], Receptores de Progesterona, business.industry, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [Medical Subject Headings], medicine.disease, Antineoplásicos, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Neoplastic Processes::Neoplasm Recurrence, Local [Medical Subject Headings], Receptores Estrogénicos, Receptor del Factor de Crecimiento Epidérmico, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Mastectomy [Medical Subject Headings], Cancer research, biology.protein, Neoplasm Grading, Neoplasm Recurrence, Local, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nuclear Proteins::Antigens, Nuclear::Ki-67 Antigen [Medical Subject Headings], business, Follow-Up Studies
Abstract

JOURNAL ARTICLE; INTRODUCTION Recurrence risk in breast cancer varies throughout the follow-up time. We examined if these changes are related to the level of expression of the proliferation pathway and intrinsic subtypes. METHODS Expression of estrogen and progesterone receptor, Ki-67, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and cytokeratin 5/6 (CK 5/6) was performed on tissue-microarrays constructed from a large and uniformly managed series of early breast cancer patients (N = 1,249). Subtype definitions by four biomarkers were as follows: luminal A (ER + and/or PR+, HER2-, Ki-67

Published
2013

36. Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis

Author

C Rodríguez-Martin, Bella Pajares, Manuel Ruiz-Borrego, Ana Lluch, MC Cámara, Miguel Martin, Eva Carrasco, Marina Pollán, Antonio Antón, Manuel Ramos, Miguel Ángel Seguí, John R. Mackey, Tadeusz Pienkowski, Olivier Tredan, Charles L. Vogel, Joaquín Gavilá, Emilio Alba, Lourdes Calvo, Álvaro Rodríguez-Lescure, Grupo Español de Investigación de Cáncer de Mama, Sanofi, Bristol-Myers Squibb, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Spanish Breast Cancer Research Group, GEICAM, [Pajares,B, Alba,E] Medical Oncology Department, Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain. [Pollán,M] Epidemiology Nacional Center, Instituto de Salud Carlos III, Madrid, Spain. [Martín,M] Medical Oncology Department, Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain. [Mackey,J] Medical Oncology Department, Medical Cross Cancer Institute, Edmonton, AB, Canada. [Lluch,A] Hematology-Oncology Department, Hospital Clínico Universitario de Valencia- INCLIVA Health Research Institute, University of Valencia, Valencia, Spain. [Gavila,J] Medical Oncology Department, Instituto Valenciano de Oncología, Valencia, Spain. [Vogel,Ch] Medical Oncology Department, Sylvester Comprehensive Cancer at Deerfield, Miller School of Medicine, Univ. of Miami- Deerfield Bch, Miami, FL, USA. [Ruiz-Borrego,M] Medical Oncology Department, Hospital Virgen del Rocío, Sevilla, Spain. [Calvo,L] Medical Oncology Department, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain. [Pienkowski,T] Medical Oncology Department, European Health Center, Otwock, Poland. [Rodríguez-Lescure,A] Medical Oncology Department, Hospital General Universitario de Elche, Alicante, Spain. [Seguí,MA] Medical Oncology Department, Corporación Sanitaria Parc Taulí, Sabadell, Spain. [Trendan,O] Medical Oncology Department, Centre Léon Bérard, Lyon, France. [Antón,A] Medical Oncology Department, Hospital Miguel Servet, Zaragoza, Spain. [Ramos,M] Medical Oncology Department, Centro Oncológico de Galicia, A Coruña, Spain. [Cámara,MdC, Rodríguez-Martín,C, Carrasco,E] Spanish Breast Cancer Research Group, GEICAM, Madrid, Spain., and This work was supported by the Spanish Breast Cancer Research Group (Grupo Español de Investigación de Cáncer de Mama) (GEICAM). No funding was received for the data analyses or the writing of this manuscript. Clinical trials GEICAM/9805 and BCIRG 001 were funded by Sanofi Aventis. GEICAM/9906 and GEICAM/2003-02 were partially funded by Bristol-Myers Squibb. These funding bodies were not involved in the collection and interpretation of the data or in the decision to publish. EA and MM were also supported by FEDER (RECTICC-RD12/0036/0076)

Subjects
Índice de Masa Corporal, Oncology, Receptor, ErbB-2, medicine.medical_treatment, Obesidad, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis [Medical Subject Headings], Supervivencia sin Enfermedad, Body Mass Index, Antineoplastic Combined Chemotherapy Protocols, Medicine, Anthracyclines, Young adult, Medicine(all), Hazard ratio, Neoplasias de la Mama, Pronóstico, Femenino, Middle Aged, Prognosis, Chemotherapy regimen, Treatment Outcome, Female, Taxoids, Mastectomy, Research Article, Adult, medicine.medical_specialty, Análisis de Supervivencia, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Breast Neoplasms, Disease-Free Survival, Young Adult, Breast cancer, Internal medicine, Adjuvant therapy, Humans, Obesity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Disease-Free Survival [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Gynecology, Dose-Response Relationship, Drug, business.industry, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [Medical Subject Headings], Retrospective cohort study, Antineoplásicos, medicine.disease, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Multivariate Analysis, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], Neoplasm Recurrence, Local, business, Body mass index
Abstract

Obesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification. METHODS: We performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003-02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype. RESULTS: Multivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype. CONCLUSIONS: Severely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes. This work was supported by the Spanish Breast Cancer Research Group (Grupo Español de Investigación de Cáncer de Mama) (GEICAM). No funding was received for the data analyses or the writing of this manuscript. Clinical trials GEICAM/9805 and BCIRG 001 were funded by Sanofi Aventis. GEICAM/9906 and GEICAM/2003-02 were partially funded by Bristol-Myers Squibb. These funding bodies were not involved in the collection and interpretation of the data or in the decision to publish. EA and MM were also supported by FEDER (RECTICC-RD12/0036/0076). We thank all the participating patients, clinicians, GEICAM and local research staff. We thank Hosanna Soler Vila, PhD, who provided medical writing services on behalf of GEICAM. Sí

Published
2013

37. MicroRNA-200 Family Modulation in Distinct Breast Cancer Phenotypes

Author

Clare M. Isacke, Begoña Vieites, José Palacios, David Sarrió, Susana Ramiro-Fuentes, María Ángeles López-García, Juan Díaz-Martín, Laura Romero-Pérez, Michele Biscuola, María Ángeles Castilla, Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica, Instituto de Biomedicina de Sevilla (IBIS), Universidad de Sevilla. Departamento de Química Orgánica, [Castilla,MÁ, Díaz-Martín,J, Romero-Pérez,L, López-García,MÁ, Vieites,B, Biscuola,M, Ramiro-Fuentes,S] Instituto de Biomedicina de Sevilla-CSIC-Universidad de Sevilla, Hospital Universitario Virgen del Rocío, Department of Pathology, Seville, Spain. [Isacke,CM] Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, United Kingdom. [Palacios,J] Hospital Universitario Ramón y Cajal, Department of Pathology, Madrid, Spain, The Instituto de Salud Carlos III (ISCIII, Grant Nos PI07/90324 and PI080971)and the Ministerio de Ciencia e Innovación (MCINN), co-financed by the European Development Regional Fund, ‘‘A way to achieve Europe’’ EDRF (Grant No. RD06/0020/0013), the Junta de Andalucía (Consejería de Salud, Grant No.PI-0384/2007, PI0581/2009), the Consejería de Innovación (Proyecto de Excelencia, Grant No. P07-CVI-03100), and Sandra Ibarra Foundation (Grant No. 2011/088) to JP. MAC and JDM are PhD researchers funded by the ISCIII (Grant No. RD06/0020/0013) and the Consejería de Salud Junta de Andalucía (PI0581/2009)

Subjects
Pathology, Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings], lcsh:Medicine, Estrogen receptor, Invasive Ductal Carcinoma, Metastasis, 0302 clinical medicine, Molecular cell biology, Breast Tumors, Basic Cancer Research, Breast, lcsh:Science, Promoter Regions, Genetic, Regulation of gene expression, 0303 health sciences, Multidisciplinary, Neoplasias de la Mama, Obstetrics and Gynecology, 3. Good health, Gene Expression Regulation, Neoplastic, Ductal Carcinoma in Situ, Phenotype, Oncology, 030220 oncology & carcinogenesis, DNA methylation, Medicine, Epigenetics, Female, Invasive Lobular Carcinoma, DNA modification, Fenotipo, Transición Epitelial-Mesenquimal, Research Article, medicine.medical_specialty, Epithelial-Mesenchymal Transition, Breast Neoplasms, Biology, 03 medical and health sciences, Breast cancer, Diagnostic Medicine, Cell Line, Tumor, microRNA, Breast Cancer, medicine, Genetics, Cancer Genetics, Humans, Epithelial–mesenchymal transition, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], 030304 developmental biology, lcsh:R, Cancers and Neoplasms, DNA, DNA Methylation, medicine.disease, MicroRNAs, Cancer research, Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Transdifferentiation::Epithelial-Mesenchymal Transition [Medical Subject Headings], lcsh:Q, Gene expression, Biomarkers, General Pathology
Abstract

The epithelial to mesenchymal transition (EMT) contributes to tumor invasion and metastasis in a variety of cancer types. In human breast cancer, gene expression studies have determined that basal-B/claudin-low and metaplastic cancers exhibit EMT-related characteristics, but the molecular mechanisms underlying this observation are unknown. As the family of miR-200 microRNAs has been shown to regulate EMT in normal tissues and cancer, here we evaluated whether the expression of the miR-200 family (miR-200f) and their epigenetic state correlate with EMT features in human breast carcinomas. We analyzed by qRT-PCR the expression of miR-200f members and various EMT-transcriptional inducers in a series of 70 breast cancers comprising an array of phenotypic subtypes: estrogen receptor positive (ER+), HER2 positive (HER2+), and triple negative (TN), including a subset of metaplastic breast carcinomas (MBCs) with sarcomatous (homologous or heterologous) differentiation. No MBCs with squamous differentiation were included. The DNA methylation status of miR-200f loci in tumor samples were inspected using Sequenom MassArray® MALDI-TOF platform. We also used two non-tumorigenic breast basal cell lines that spontaneously undergo EMT to study the modulation of miR-200f expression during EMT in vitro. We demonstrate that miR-200f is strongly decreased in MBCs compared with other cancer types. TN and HER2+ breast cancers also exhibited lower miR-200f expression than ER+ tumors. Significantly, the decreased miR-200f expression found in MBCs is accompanied by an increase in the expression levels of EMT-transcriptional inducers, and hypermethylation of the miR-200c-141 locus. Similar to tumor samples, we demonstrated that downregulation of miR-200f and hypermethylation of the miR-200c-141 locus, together with upregulation of EMT-transcriptional inducers also occur in an in vitro cellular model of spontaneous EMT. Thus, the expression and methylation status of miR-200f could be used as hypothetical biomarkers to assess the occurrence of EMT in breast cancer. © 2012 Castilla et al., This work was supported by grants from: the Instituto de Salud Carlos III (ISCIII; Grant Nos PI07/90324 and PI080971) and the Ministerio de Ciencia e Innovación (MCINN), co-financed by the European Development Regional Fund, “A way to achieve Europe” EDRF (Grant No. RD06/0020/0013); the Junta de Andalucía (Consejería de Salud, Grant No.PI-0384/2007, PI0581/2009); the Consejería de Innovación (Proyecto de Excelencia, Grant No. P07-CVI-03100); and Sandra Ibarra Foundation (Grant No. 2011/088) to JP. MAC and JDM are PhD researchers funded by the ISCIII (Grant No. RD06/0020/0013) and the Consejería de Salud, Junta de Andalucía (PI0581/2009), respectively. DS was funded by an EU Marie Curie Intra-European Fellowship (PIEF-GA-2008-221083) and by Breakthrough Breast Cancer. LRP is a PhD student recipient of a PFIS fellowship (Grant No. F109/00193). MB is a researcher funded by the ISCIII-Red de Biobancos RD09/0076/00085. SR works as a lab technician supported by the ISCIII (PI080971). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Published
2012

38. Effectiveness of Core Stability Exercises and Recovery Myofascial Release Massage on Fatigue in Breast Cancer Survivors: A Randomized Controlled Clinical Trial

Author

César Fernández-de-las-Peñas, Manuel Arroyo-Morales, Rosario del Moral-Avila, María Belén Feriche-Fernández-Castanys, Irene Cantarero-Villanueva, Carolina Fernández-Lao, [Cantarero-Villanueva,I, Fernández-Lao,C, Arroyo-Morales,M] Department of Physical Therapy, Health Sciences Faculty, University of Granada, Granada, Spain. [Moral-Avila,R del] Radiotherapy Breast Oncology Unit, University Hospital Virgen de las Nieves, Granada, Spain. [Fernández-de-Las-Peñas,C] Department of Physical Therapy, Occupational Therapy, Rehabilitation, and Physical Medicine, King Juan Carlos university, Alcorcón, Spain. [Feriche-Fernández-Castanys,MB] Physical Education Department, Faculty of Sciences, Physical Activity, and Sports, University of Granada, Granada, Spain., and The paper was funded by a Research Project Grant (FIS ETES-PI0890418 and 10/02749) from the Health Institute Carlos III and PN I+D+I 2008–2011, Madrid, Spanish. Government and a Grant of Andalusian Health Service, Junta de Andalucia (PI-0457-2010).

Subjects
medicine.medical_specialty, Article Subject, Terapia por Ejercicio, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Physical Therapy Modalities::Musculoskeletal Manipulations::Massage [Medical Subject Headings], Named Groups::Persons::Survivors [Medical Subject Headings], Masaje, Sobrevivientes, Breast cancer, Physical medicine and rehabilitation, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Fatigue [Medical Subject Headings], medicine, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Depression (differential diagnoses), Massage, Fatiga, business.industry, Neoplasias de la Mama, Femenino, Core stability, Ensayos Clínicos Controlados Aleatorios como Asunto, lcsh:Other systems of medicine, lcsh:RZ201-999, medicine.disease, Trunk, Myofascial release, Clinical trial, Check Tags::Female [Medical Subject Headings], Complementary and alternative medicine, Physical therapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Physical Therapy Modalities::Exercise Therapy [Medical Subject Headings], business, After treatment, Research Article
Abstract

The purpose of the present paper was to evaluate the effects of an 8-week multimodal program focused on core stability exercises and recovery massage with DVD support for a 6-month period in physical and psychological outcomes in breast cancer survivors. A randomized controlled clinical trial was performed. Seventy-eight (n=78) breast cancer survivors were assigned to experimental (core stability exercises plus massage-myofascial release) and control (usual health care) groups. The intervention period was 8 weeks. Mood state, fatigue, trunk curl endurance, and leg strength were determined at baseline, after the last treatment session, and at 6 months of followup. Immediately after treatment and at 6 months, fatigue, mood state, trunk curl endurance, and leg strength exhibited greater improvement within the experimental group compared to placebo group. This paper showed that a multimodal program focused on core stability exercises and massage reduced fatigue, tension, depression, and improved vigor and muscle strength after intervention and 6 months after discharge.

Published
2012
Full Text
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39. Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study

Author

Elio Riboli, Sabina Sieri, Sabina Rinaldi, Birgit Teucher, Petra H.M. Peeters, José Ramón Quirós, Rudolf Kaaks, Rebecca Ritte, María José Sánchez, Kim Overvad, Isabelle Romieu, Sanda Krum-Hansen, Franco Berrino, Naomi E. Allen, Françoise Clavel-Chapelon, Genevieve Buckland, Salvatore Panico, Anja Olsen, Afshan Siddiq, Heiner Boeing, David Cox, Eiliv Lund, Krasimira Aleksandrova, Malin Sund, Per Lenner, Rosario Tumino, Nicholas J. Wareham, Agnès Fournier, Annekatrin Lukanova, Eva Ardanaz, Carla H. van Gils, Pagona Lagiou, Inger T. Gram, Bas Bueno-de-Mesquita, Paolo Vineis, Sabine Rohrmann, Guy Fagherazzi, Thure Filskov Overvad, Antonia Trichopoulou, María Dolores Chirlaque, Pilar Amiano, Kay-Tee Khaw, Domenico Palli, Dimitrios Trichopoulos, Timothy J. Key, Anne Tjønneland, Laure Dossus, Ritte, R, Lukanova, A, Berrino, F, Dossus, L, Tj?nneland, A, Olsen, A, Overvad, Tf, Overvad, K, Clavel Chapelon, F, Fournier, A, Fagherazzi, G, Rohrmann, S, Teucher, B, Boeing, H, Aleksandrova, K, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Palli, D, Sieri, S, Panico, Salvatore, Tumino, R, Vineis, P, Quir?s, Jr, Buckland, G, S?nchez, Mj, Amiano, P, Chirlaque, Md, Ardanaz, E, Sund, M, Lenner, P, Bueno de Mesquita, B, van Gils, Ch, Peeters, Ph, Krum Hansen, S, Gram, It, Lund, E, Khaw, Kt, Wareham, N, Allen, Ne, Key, Tj, Romieu, I, Rinaldi, S, Siddiq, A, Cox, D, Riboli, E, Kaaks, R., Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Preventive and Predictive Medicine, Fondazione IRCCS Instituto Nazionale dei Tumori, Cancer Epidemiology Institute, Danish Cancer Society, Department of Cardiology, Aarhus University [Aarhus], Department of Epidemiology, Aarhus University [Aarhus]-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, German Institute of Human Nutrition, Hellenic Health Foundation, WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene-Epidemiology and Medical Statistics-Athens Medical School, Harvard School of Public Health, Bureau of Epidemiologic Research, Academy of Athens, Molecular and Nutritional Epidemiology Unit, Scientific Institute of Tuscany-Cancer Research and Prevention Institute (ISPO), Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II-Medical School, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, Centre for Environment and Health, Imperial College London-School of public health, Human Genetics Foundation (HuGeF), Università degli studi di Torino (UNITO), Public Health and Health Planning Directorate, Universidad de Oviedo, Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL)-Cancer Epidemiology Research Programme, Granada Cancer Registry, Andalusian School of Public Health [Granada], Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Public Health Division of Gipuzkoa, Institute BIO Donostia-Health Department, Murcia Regional Health Authority, Navarra Public Health Institute, Leyre 15, Department of Surgery and Perioperative Sciences, Umea University Hospital, Department of Oncology and Radiation Sciences, Oncology, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Centre, Julius Center for Health Sciences and Primary Care, VU University Medical Center [Amsterdam], Department of Epidemiology and Biostatistics, Imperial College London-Faculty of Medicine-School of public health, Institute of Community Medicine, University of Tromsø (UiT), School of Clinical Medicine, University of Cambridge [UK] (CAM), Medical Research Council, Addenbrooke's Hospital-Epidemiology Unit, Cancer Epidemiology Unit, University of Oxford [Oxford], Unité d'épidémiologie nutritionnelle, Section Nutrition et Métabolisme-Centre Internationale de la recherche sur le cancer (CIRC), Department of Genomics of Common Disease, This work was (partly) supported by a grant from the German Research Foundation, Graduiertenkolleg 793: Epidemiology of communicable and chronic noncommunicable diseases and their interrelationships. The coordination of EPIC is financially supported by the European Commission Directorate General for Health and Consumer Protection (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue contre le Cancer, Mutuelle Générale de l'Education Nationale, and the Institut National de la Santé et de la Recherche Médicale (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and the Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity, the Italian Association for Research on Cancer (AIRC) and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sport (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, the Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway), the Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (number 6236) and Navarra, and ISCIII RTICC Red Temática de Investigación Cooperativa en Cáncer (R06/0020) (Spain), the Swedish Cancer Society, Swedish Scientific Council and the Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, and the Medical Research Council, (United Kingdom)., [Ritte,R, Lukanova,A, Dossus,L, Rohrmann,S, Teucher,B, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Berrino,F] Department of Ritte et al. Breast Cancer Research Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tjønneland,A, Olsen,A] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Overvad,TF] Department of Cardiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. [Overvad,K] Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark. [Clavel-Chapelon,F, Fournier,A, Fagherazzi,G] Centre for Research in Epidemiology and Population Health, INSERM, Institut Gustave Roussy, Villejuif, France. Paris South University, Villejuif, France. [Rohrmann,S] Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, Zurich, Switzerland. [Boeing,H, Aleksandrova,K] Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Lagiou,P] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Goudi, Athens, Greece. [Trichopoulou, A] Hellenic Health Foundation, Athens, Greece. [Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, USA. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Scientific Institute of Tuscany, Florence, Italy. [Sieri,S] Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. [Panico,S] Department of Clinical and Experimental Medicine Medical School Federico II University, Naples, Italy. [Tumino, R] Cancer Registry and Histopathology Unit, ‘Civile M.P. Arezzo’ Hospital ASP 7, Ragusa, Italy. [Vineis,P, Riboli,E] Centre for Environment and Health School of Public Health, Imperial College London, London, UK. [Vineis,P] Human Genetics Foundation (HuGeF), Torino, Italy. [Quirós,JR] Public Health and Health Planning Directorate, Asturias, Spain. [Buckland,G] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Sánchez,MJ] Andalusian School of Public Health, Granada, Spain. [Sánchez,MJ, Amiano,P, Chirlaque,MD, Ardanaz,E] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Amiano,P] Public Health Division of Gipuzkoa, Institute BIO Donostia, Health Department, Basque Region, Gipuzkoa, Spain. [Chirlaque,MD] Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Sund,M] Department of Surgery and Perioperative Sciences, Umeå University Hospital, Umeå, Sweden. [Lenner,P] Department of Oncology and Radiation Sciences, Oncology, Umeå University Hospital, Umeå, Sweden. [Bueno-de-Mesquita,B] National Institute for Public Health and the Environment, Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [van Gils,CH, Peeters,PHM] Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands. [Peeters,PHM, Siddiq,A, Cox,D] Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College, London, London, UK. [Krum-Hansen,S, Gram,IT, Lund,E] Institute of Community Medicine, University of Tromsø, Tromsø, Norway. [Khaw,KT] School of Clinical Medicine, University of Cambridge, The Old Schools, Trinity Lane, Cambridge, UK. [Wareham,N] Medical Research Council, Epidemiology Unit, Addenbrooke’s Hospital, Cambridge, UK. [Allen,NE, Key,TJ] Cancer Epidemiology Unit, University of Oxford, Oxford, UK. [Romieu,I, Rinaldi,S] Nutritional Epidemiology Group, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France. [Siddiq,A] Department of Genomics of Common Disease, School of Public Health, Imperial College London, London UK., University of Zurich, Kaaks, Rudolf, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical School-University of Naples Federico II = Università degli studi di Napoli Federico II, Università degli studi di Torino = University of Turin (UNITO), Universidad de Oviedo [Oviedo], University of Oxford, and BMC, Ed.

Subjects
Oncology, medicine.medical_treatment, body-mass index, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Body Mass Index, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Medicine, 1306 Cancer Research, Prospective Studies, Adiposity, estrogen-receptor, Aged, 80 and over, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Age Factors [Medical Subject Headings], 3. Good health, Postmenopause, nutrition, Receptors, Estrogen, PREMENOPAUSAL WOMEN, Adiposidad, premenopausal omen, fat distribution, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk [Medical Subject Headings], 030220 oncology & carcinogenesis, Cohort, 2730 Oncology, Receptors, Progesterone, Factores de riesgo, Cohort study, medicine.medical_specialty, Named Groups::Persons::Age Groups::Adult::Young Adult [Medical Subject Headings], Estudios de cohortes, united-states, 03 medical and health sciences, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Humans, Aged, Gynecology, Cancer och onkologi, Science & Technology, Proportional hazards model, weight, ONCOLOGY, medicine.disease, Check Tags::Female [Medical Subject Headings], Premenopause, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer and Oncology, Surgery, Body mass index, Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings], postmenopausal women, Overweight, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Fat Distribution::Adiposity [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Cohort Studies, Risk Factors, 030212 general & internal medicine, Prospective cohort study, physical-activity, 2. Zero hunger, Medicine(all), Estrogen Replacement Therapy, Age Factors, Hormone replacement therapy (menopause), Estudios Prospectivos, Middle Aged, POSTMENOPAUSAL WOMEN, Neoplasias de la mama, NUTRITION, Female, medicine.symptom, Life Sciences & Biomedicine, Research Article, Factores de Edad, Adult, Risk, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Climacteric::Menopause::Premenopause [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Hormone Replacement Therapy::Estrogen Replacement Therapy [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone [Medical Subject Headings], UNITED-STATES, 610 Medicine & health, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, size, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [Medical Subject Headings], Young Adult, Internal medicine, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Receptores de Progesterona, business.industry, Kirurgi, FAT DISTRIBUTION, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), Receptores Estrogénicos, BODY-MASS INDEX, ESTROGEN-RECEPTOR, PHYSICAL-ACTIVITY, SIZE, WEIGHT, business
Abstract

Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't; INTRODUCTION Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use. METHODS Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed. RESULTS For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ≤49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ≥65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ≤22.5 kg/m2) than for more overweight women (BMI ≥25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime. CONCLUSIONS An elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors. Yes

Published
2012
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40. Combined low initial DNA damage and high radiation-induced apoptosis confers clinical resistance to long-term toxicity in breast cancer patients treated with high-dose radiotherapy

Author

Ruth Carmona-Vigo, Beatriz Pinar, María Isabel Núñez, Pedro C. Lara, Carlos Rodríguez-Gallego, Elisa Bordón, Marta Lloret, Luis Alberto Henríquez-Hernández, [Henríquez-Hernández,L.A, Carmona-Vigo,R, Pinar,B, Bordón,E, Lloret,M, Lara,PC] Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr.Negrín, Spain. [Henríquez-Hernández,L.A, Rodríguez-Gallego,C, Lara,PC] Instituto Canario de Investigación del Cáncer (ICIC), Spain. [Henríquez-Hernández,L.A, Lara,PC] Clinical Sciences Department, Universidad de Las Palmas de Gran Canaria, Spain. [Núñez, M. I] Radiology Department, Hospital Universitario San Cecilio, Granada, Spain. [Rodríguez-Gallego, C.] Immunology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Spain., and This work was subsidized by a grant from the Ministerio de Educación y Ciencia (CICYT: SAF 2004-00889) and Fundación del Instituto Canario de Investigación del Cáncer (FICIC).

Subjects
Named Groups::Persons::Adult Children [Medical Subject Headings], medicine.medical_treatment, ADN, Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings], Apoptosis, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Radiation Tolerance, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Mediana Edad, Lymphocytes, Prospective cohort study, Aged, 80 and over, Adulto, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Radiotherapy [Medical Subject Headings], Neoplasias de la Mama, Linfocitos, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Humanos, Treatment Outcome, 320101 Oncología, Daño del ADN, Oncology, Radiology Nuclear Medicine and imaging, Femenina, Toxicity, Female, Adult, lcsh:Medical physics. Medical radiology. Nuclear medicine, medicine.medical_specialty, DNA damage, Resultado del Tratamiento, lcsh:R895-920, Anciano, Urology, Breast Neoplasms, lcsh:RC254-282, Phenomena and Processes::Physiological Phenomena::Physiological Processes::Radiation Tolerance::Dose-Response Relationship, Radiation [Medical Subject Headings], Breast cancer, Radioterapia, medicine, Humans, Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes [Medical Subject Headings], Radiology, Nuclear Medicine and imaging, Radiosensitivity, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings], Tolerancia a Radiación, Radiotherapy, Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Damage [Medical Subject Headings], business.industry, Relación Dosis-Respuesta en la Radiación, Research, Dose fractionation, Dose-Response Relationship, Radiation, DNA, medicine.disease, Anciano de 80 o más Años, Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Physiological Processes::Radiation Tolerance [Medical Subject Headings], Radiation therapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Radiotherapy::Radiotherapy Dosage::Dose Fractionation [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Dose Fractionation, Radiation, Nuclear medicine, business, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA [Medical Subject Headings], DNA Damage, Fraccionamiento de la Dosis
Abstract

Background Either higher levels of initial DNA damage or lower levels of radiation-induced apoptosis in peripheral blood lymphocytes have been associated to increased risk for develop late radiation-induced toxicity. It has been recently published that these two predictive tests are inversely related. The aim of the present study was to investigate the combined role of both tests in relation to clinical radiation-induced toxicity in a set of breast cancer patients treated with high dose hyperfractionated radical radiotherapy. Methods Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma treated with high-dose hyperfractioned radical radiotherapy. Acute and late cutaneous and subcutaneous toxicity was evaluated using the Radiation Therapy Oncology Group morbidity scoring schema. The mean follow-up of survivors (n = 13) was 197.23 months. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radiation-induced apoptosis (RIA) at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. Results Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). Radiation-induced apoptosis increased with radiation dose (median 12.36, 17.79 and 24.83 for 1, 2, and 8 Gy respectively). We observed that those "expected resistant patients" (DSB values lower than 1.78 DSB/Gy per 200 Mbp and RIA values over 9.58, 14.40 or 24.83 for 1, 2 and 8 Gy respectively) were at low risk of suffer severe subcutaneous late toxicity (HR 0.223, 95%CI 0.073-0.678, P = 0.008; HR 0.206, 95%CI 0.063-0.677, P = 0.009; HR 0.239, 95%CI 0.062-0.929, P = 0.039, for RIA at 1, 2 and 8 Gy respectively) in multivariate analysis. Conclusions A radiation-resistant profile is proposed, where those patients who presented lower levels of initial DNA damage and higher levels of radiation induced apoptosis were at low risk of suffer severe subcutaneous late toxicity after clinical treatment at high radiation doses in our series. However, due to the small sample size, other prospective studies with higher number of patients are needed to validate these results.

Published
2011

41. The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53- Independent Manner in Colon and Breast Cancer Cells

Author

Mariano Esteban, María Ángel García, Antonia Aránega, Margarita Aguilera, Joaquín M. Campos, Esther Carrasco, Jose Prados, Carmen Rivas, Miguel Angel Calleja, Pablo J. Álvarez, Juan A. Marchal, [García,MA] Unidad de Investigación, Hospital Universitario Virgen de las Nieves, Granada, Spain.[Aguilera,M] Unidad de Farmacogenética, Hospital Universitario Virgen de las Nieves, Granada, Spain.[García,MA, Carrasco,E, Alvarez,P, Prados,JC, Marchal,JA, Aránega,A] Instituto de Biopatología y Medicina Regenerativa (IBIMER), Universidad de Granada,Granada, Spain. [Rivas,C] Centro Nacional de Biotecnología, CSIC, Madrid,Spain. [Campos,JM] Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Granada, Spain., and This work was supported in part by grants from the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria projects n°. CP08/0063, PI07/0527 and PI10/02295). No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Subjects
Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor [Medical Subject Headings], Colorectal cancer, Cancer Treatment, lcsh:Medicine, Apoptosis, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], eIF-2 Kinase, Breast cancer, Molecular Cell Biology, Cytotoxic T cell, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidinones::Uracil::Fluorouracil [Medical Subject Headings], Flow cytometry, Phosphorylation, lcsh:Science, Phenomena and Processes::Metabolic Phenomena::Metabolism::Phosphorylation [Medical Subject Headings], Cellular Stress Responses, Multidisciplinary, biology, medicine.diagnostic_test, Cell Death, Chemistry, Colon Adenocarcinoma, Neoplasias de la Mama, Femenino, Obstetrics and Gynecology, Humanos, Antimetabolitos Antineoplásicos, Oncology, Cancer treatment, Colonic Neoplasms, Medicine, Female, Fluorouracil, Fosforilación, Research Article, Programmed cell death, Antimetabolites, Antineoplastic, Drugs and Devices, Colon, Breast Neoplasms, Gastroenterology and Hepatology, eIF-2 Quinasa, Cell Line, Tumor, Breast Cancer, Gastrointestinal Tumors, medicine, Humans, Protein kinase A, Biology, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], EIF-2 kinase, lcsh:R, Neoplasias del Colon, Cancers and Neoplasms, Chemotherapy and Drug Treatment, medicine.disease, Protein kinase R, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::eIF-2 Kinase [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Antimetabolites::Antimetabolites, Antineoplastic [Medical Subject Headings], SW480 cells, Línea Celular Tumoral, Immunology, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Colonic Neoplasms [Medical Subject Headings], Cancer research, biology.protein, lcsh:Q, Tumor Suppressor Protein p53
Abstract

The chemotherapeutic drug 5-FU is widely used in the treatment of a range of cancers, but resistance to the drug remains a major clinical problem. Since defects in the mediators of apoptosis may account for chemo-resistance, the identification of new targets involved in 5-FU-induced apoptosis is of main clinical interest. We have identified the ds-RNA-dependent protein kinase (PKR) as a key molecular target of 5-FU involved in apoptosis induction in human colon and breast cancer cell lines. PKR distribution and activation, apoptosis induction and cytotoxic effects were analyzed during 5-FU and 5-FU/IFNα treatment in several colon and breast cancer cell lines with different p53 status. PKR protein was activated by 5-FU treatment in a p53-independent manner, inducing phosphorylation of the protein synthesis translation initiation factor eIF-2α and cell death by apoptosis. Furthermore, PKR interference promoted a decreased response to 5-FU treatment and those cells were not affected by the synergistic antitumor activity of 5-FU/IFNα combination. These results, taken together, provide evidence that PKR is a key molecular target of 5-FU with potential relevance in the clinical use of this drug., This work was supported in part by grants from the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria projects n°. CP08/0063, PI07/0527 and PI10/02295).

Published
2011

42. Radiation induced apoptosis and initial DNA damage are inversely related in locally advanced breast cancer patients

Author

Elisa Bordón, Marta Lloret, María Isabel Núñez, Pedro C. Lara, Carlos Rodríguez-Gallego, Beatriz Pinar, Mariano Ruiz de Almodóvar, Luis Alberto Henríquez-Hernández, [Pinar B, Lara PC, Lloret M] Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Spain. [Pinar B, Henríquez-Hernández LA, Bordon E, Rodriguez-Gallego C, Lloret M] Instituto Canario de Investigación del Cáncer (ICIC), Spain. [Henríquez-Hernández LA] Clinical Sciences Department, Universidad de Las Palmas de Gran Canaria, Spain. [Rodriguez-Gallego C] Immunology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Spain. [Nuñes, MI, and Ruiz de Almodovar, M] Radiology Department, Hospital Universitario San Cecilio, Universidad de Granada, Spain.

Subjects
Pathology, medicine.medical_treatment, Apoptosis, Cell Separation, Radiation Tolerance, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, DNA Breaks, Double-Stranded, Citometría de Flujo, medicine.diagnostic_test, Neoplasias de la Mama, Femenino, Roturas del ADN de Doble Cadena, Flow Cytometry, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Humanos, 320101 Oncología, Oncology, Radiology Nuclear Medicine and imaging, Toxicity, Female, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Neoplasm Staging [Medical Subject Headings], Phenomena and Processes::Physical Phenomena::Electromagnetic Phenomena::Radiation::Radiation Tolerance [Medical Subject Headings], lcsh:Medical physics. Medical radiology. Nuclear medicine, medicine.medical_specialty, DNA damage, lcsh:R895-920, Locally advanced, Breast Neoplasms, lcsh:RC254-282, Flow cytometry, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Cytological Techniques::Cell Separation [Medical Subject Headings], Breast cancer, Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Damage::DNA Breaks::DNA Breaks, Double-Stranded [Medical Subject Headings], medicine, Humans, Radiology, Nuclear Medicine and imaging, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Photometry::Luminescent Measurements::Fluorometry::Cytophotometry::Flow Cytometry [Medical Subject Headings], Separación Celular, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Neoplasm Staging, Tolerancia a Radiación, Anatomy::Urogenital System::Genitalia::Genitalia, Female [Medical Subject Headings], business.industry, Research, medicine.disease, Estadificación de Neoplasias, Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis [Medical Subject Headings], Radiation therapy, chemistry, Cancer research, business, DNA
Abstract

Background. DNA-damage assays, quantifying the initial number of DNA double-strand breaks induced by radiation, have been proposed as a predictive test for radiation-induced toxicity. Determination of radiation-induced apoptosis in peripheral blood lymphocytes by flow cytometry analysis has also been proposed as an approach for predicting normal tissue responses following radiotherapy. The aim of the present study was to explore the association between initial DNA damage, estimated by the number of double-strand breaks induced by a given radiation dose, and the radio-induced apoptosis rates observed. Methods. Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radio-induced apoptosis at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. Results. Radiation-induced apoptosis increased in order to radiation dose and data fitted to a semi logarithmic mathematical model. A positive correlation was found among radio-induced apoptosis values at different radiation doses: 1, 2 and 8 Gy (p < 0.0001 in all cases). Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). A statistically significant inverse correlation was found between initial damage to DNA and radio-induced apoptosis at 1 Gy (p = 0.034). A trend toward 2 Gy (p = 0.057) and 8 Gy (p = 0.067) was observed after 24 hours of incubation. Conclusions. An inverse association was observed for the first time between these variables, both considered as predictive factors to radiation toxicity. Yes Daños en el ADN-ensayos, cuantificando el número inicial de ADN de doble cadena se rompe inducida por la radiación, se han propuesto como una prueba predictiva para la radiación inducida por la toxicidad. Determinación de la apoptosis inducida por radiación en linfocitos de sangre periférica mediante el análisis de citometría de flujo también ha sido propuesta como un método para predecir las respuestas normales del tejido después de la radioterapia. El objetivo del presente estudio fue explorar la asociación entre el daño del ADN inicial, estimada por el número de doble filamento se rompe inducida por una dosis de radiación que se administra, y se observaron las tasas de la apoptosis inducida por la radio. MÉTODOS: Linfocitos de sangre periférica fueron tomadas de 26 pacientes consecutivos con carcinoma de mama localmente avanzado. Radiosensibilidad de los linfocitos se cuantificó como el número inicial de ADN de doble cadena se rompe inducida por Gy y la unidad de ADN por (200 Mbps). Radio inducida por la apoptosis en Gy 1, 2 y 8 se midió por citometría de flujo utilizando anexina V / ioduro de propidio. RESULTADOS: La radiación inducida por aumento de la apoptosis con el fin de dosis de radiación y de datos instalados en un modelo matemático semi logarítmica. Una correlación positiva se encontró entre los valores de la apoptosis inducida por la radio a diferentes dosis de radiación: 1, 2 y 8 Gy (p

Published
2010

43. Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition

Author

Isabel García-Real, José Palacios, Cristina Sánchez, Clara Andradas, Manuel Guzmán, Gema Moreno-Bueno, María M. Caffarel, Emilia Mira, Santos Mañes, Eduardo Pérez-Gómez, Camilla Cerutti, Juana M. Flores, [Caffarel,MM, Andradas,C, Pérez-Gómez,E, Cerutti,C, Guzmán,M, Sánchez,C] Dept. Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain. [Mira,E, Mañes,S] Dept. Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain. [Moreno-Bueno,G] Dept. Biochemistry, School of Medicine, Universidad Autónoma-Instituto de Investigaciones Biomédicas 'Alberto Sols', IdiPaz, Madrid, Spain. [Flores,JM, García-Real,I] Dept. Animal Surgery and Medicine, School of Veterinary, Complutense University, Madrid, Spain. [Palacios,J] Servicio de Anatomía Patológica, Hospital Virgen del Rocío, Seville, Spain. [Caffarel,MM] Dept. Pathology, University of Cambridge, United Kingdom, CC, Dept. Life Sciences, The Open University, Milton Keynes, UK., and This study was supported by grants from Fondo de Investigaciones Sanitarias (PI080253 to CS and PI086080971 to JP), Ministerio de Ciencia e Innovación (SAF2006-00918 to MG, SAF2007-63075 to GMB and SAF2008-00649 to SM), RETICS (RD06/0020/0013 to JP), Fundación Mutua Madrileña (to CS and to GMB), Consejería de Innovación Junta de Andalucía (to JP), the Marató TV3 Foundation (053132 to SM) and GW Pharmaceuticals/Otsuka Pharmaceuticals (to CS).

Subjects
Oncology, Cancer Research, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors [Medical Subject Headings], Receptor, ErbB-2, Progresión de la Enfermedad, medicine.medical_treatment, Proteínas Proto-Oncogénicas c-akt, ComputingMilieux_LEGALASPECTSOFCOMPUTING, Receptor, Cannabinoid, CB2, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, erbB-2 [Medical Subject Headings], Trastuzumab, Medicine, Neoplasm Metastasis, Receptor erbB-2, skin and connective tissue diseases, education.field_of_study, Femenino, Neoplasias de la Mama, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB2 [Medical Subject Headings], Metastatic breast cancer, Humanos, Cannabinoides, Disease Progression, Inhibidores de las Proteína Quinasas, Molecular Medicine, Female, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Terpenes::Cannabinoids [Medical Subject Headings], medicine.drug, Agonist, medicine.medical_specialty, medicine.drug_class, Population, Down-Regulation, Breast Neoplasms, lcsh:RC254-282, Breast cancer, Internal medicine, Diseases::Neoplasms::Neoplastic Processes::Neoplasm Metastasis [Medical Subject Headings], Humans, education, Protein kinase B, Protein Kinase Inhibitors, PI3K/AKT/mTOR pathway, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Progression [Medical Subject Headings], Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Down-Regulation [Medical Subject Headings], Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::Proto-Oncogene Proteins c-akt [Medical Subject Headings], business.industry, Cannabinoids, Research, Metástasis de la Neoplasia, Regulación hacia Abajo, medicine.disease, Receptor Cannabinoide CB2, Check Tags::Female [Medical Subject Headings], Cannabinoid, business, Proto-Oncogene Proteins c-akt
Abstract

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al., [Background]: ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors. [Results]: Our results show that both Delta(9)-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2. [Conclusions]: Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.

Published
2010

44. Hypermethylated 14-3-3-σ and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis

Author

José Luis Linares-Fernández, Rosario Del Moral, M. Zurita, Sandra Ríos Arrabal, Blanca Torres, Joaquina Martínez-Galán, Francisco Javier Oliver, Pedro C. Lara, José Mariano Ruiz de Almodóvar, [Zurita,M, Moral,R del, Martínez-Galán,J] Radiation Oncology, Hospital Virgen de las Nieves, Granada, Spain. [Lara,PC] Instituto Canario de Investigación del Cáncer and Servicio de Oncología Radioterápica, Hospital Dr. Negrín, Gran Canaria, Spain. [Torres,B] CIBER de Epidemiología y Salud Pública, Hospital Universitario San Cecilio, Granada, Spain. [Linares-Fernández,JL, Ríos Arrabal,S, Ruiz de Almodóvar,JM] Center for Biomedical Research and Institute of Biopathology and Regenerative Medicine, Granada University, Granada, Spain. [Oliver,FJ] Instituto de Parasitología y Biomedicina, López-Neira, CSIC, Granada, Spain. [Ruiz de Almodóvar,JM] Hospital Universitario San Cecilio, Granada, Spain., This study was supported by a grant from the Ministerio de Ciencia e Innovación: SAF 2004-00889, and JL Linares is supported by the Junta de Andalucía (P06-CTS-1385).

Subjects
Oncology, CA15-3, Exonucleases, Cancer Research, Time Factors, Exonucleasas, Phenomena and Processes::Physical Phenomena::Time::Time Factors [Medical Subject Headings], España, Supervivencia sin Enfermedad, medicine.disease_cause, Polymerase Chain Reaction, Metastasis, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Breast cancer, Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Methylation [Medical Subject Headings], Promoter Regions, Genetic, Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Proteínas de Neoplasias, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA::DNA, Neoplasm [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen::Estrogen Receptor alpha [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::Adaptor Proteins, Signal Transducing::14-3-3 Proteins [Medical Subject Headings], ADN de Neoplasias, Neoplasias de la Mama, Femenino, Cancer metastasis, DNA, Neoplasm, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Metastatic breast cancer, Humanos, Neoplasm Proteins, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Sensitivity and Specificity::Predictive Value of Tests [Medical Subject Headings], Treatment Outcome, Chemotherapy, Adjuvant, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis::Disease-Free Survival [Medical Subject Headings], Female, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Neoplasm Staging [Medical Subject Headings], Breast carcinoma, Metilación de ADN, Research Article, medicine.medical_specialty, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins [Medical Subject Headings], Resultado del Tratamiento, Breast Neoplasms, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Chemotherapy, Adjuvant [Medical Subject Headings], lcsh:RC254-282, Disease-Free Survival, Predictive Value of Tests, Internal medicine, Carcinoma, medicine, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma [Medical Subject Headings], Chemicals and Drugs::Biological Factors::Biological Markers [Medical Subject Headings], Biomarkers, Tumor, Genetics, Humans, Estrogen Receptor1 (ER1), Regiones Promotoras Genéticas, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings], Neoplasm Staging, Valor Predictivo de las Pruebas, business.industry, Receptor alfa de Estrógeno, Estrogen Receptor alpha, Cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction [Medical Subject Headings], Proteinas 14-3-3, DNA Methylation, medicine.disease, Estadificación de Neoplasias, Treatment, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Exonucleases [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], 14-3-3 Proteins, Spain, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Exoribonucleases, Reacción en Cadena de la Polimerasa, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Gene Components::Regulatory Elements, Transcriptional::Promoter Regions, Genetic [Medical Subject Headings], Quimioterapia, business, Carcinogenesis, Estudios de Cohortes, Factores de Tiempo, Biomarkers
Abstract

9 páginas, 5 figuras, 2 tablas.-- et al., [Methods]: We studied two cohorts of patients: 77 patients treated for breast cancer with no signs of disease, and 34 patients with metastatic breast cancer. DNA was obtained from serum samples, and promoter methylation status was determined by using DNA bisulfite modification and quantitative methylation-specific PCR. [Results]: Serum levels of methylated gene promoter 14-3-3-σ significantly differed between Control and Metastatic Breast Cancer groups (P < 0.001), and between Disease-Free and Metastatic Breast Cancer groups (P < 0.001). The ratio of the 14-3-3-σ level before the first chemotherapy cycle to the level just before administration of the second chemotherapy cycle was defined as the Biomarker Response Ratio [BRR]. We calculated BRR values for the "continuous decline" and "rise-and-fall" groups. Subsequent ROC analysis showed a sensitivity of 75% (95% CI: 47.6 - 86.7) and a specificity of 66.7% (95% CI: 41.0 - 86.7) to discriminate between the groups for a cut-off level of BRR = 2.39. The area under the ROC curve (Z = 0.804 ± 0.074) indicates that this test is a good approach to post-treatment prognosis. [Conclusions]: The relationship of 14-3-3-σ with breast cancer metastasis and progression found in this study suggests a possible application of 14-3-3-σ as a biomarker to screen for metastasis and to follow up patients treated for metastatic breast cancer, monitoring their disease status and treatment response., This study was supported by a grant from the Ministerio de Ciencia e Innovación: SAF 2004-00889; JL Linares is supported by the Junta de Andalucía (P06-CTS-1385).

Published
2010

45. Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer

Author

Elena Gallego, Vanessa de Luque, Nuria Ribelles, Luis Vicioso, José Manuel Lozano, Emilio Alba, Alfonso Sánchez-Muñoz, Luis G. Perez-Rivas, [Sánchez-Muñoz,A, Ribelles Entrena,N, Alba Conejo,E] Servicio de Oncología Médica, Hospital Universitario Virgen de la Victoria, Málaga, España. [Gallego Domínguez,E, Vicioso Recio,L] Servicio de Anatomía Patológica, Hospital Universitario Virgen de la Victoria, Málaga, España. [Sánchez-Muñoz,A, Gallego Domínguez,EM, Luque,V de, Pérez-Rivas,LG, Vicioso Recio,L, Lozano Castro,J, Alba Conejo,E] Laboratorio de Investigación Biomédica (LIB-IMABIS), Hospital Universitario Virgen de la Victoria, Málaga, España. [Lozano Castro,J] Dpto. de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, España., and This work was supported by Fondo de Investigaciones Sanitarias grant PI081797 (to E. A.) and Ministerio de Ciencia e Innovación grant BFU2007-66100 (to J. L.).

Subjects
Cancer Research, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors [Medical Subject Headings], Colorectal cancer, Receptor, ErbB-2, KRAS protein, human, Marcadores tumorales, DNA Mutational Analysis, medicine.disease_cause, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Acid Anhydride Hydrolases::GTP Phosphohydrolases::GTP-Binding Proteins::Monomeric GTP-Binding Proteins::ras Proteins [Medical Subject Headings], Polymerase Chain Reaction, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, erbB-2 [Medical Subject Headings], KRT5 protein, human, Surgical oncology, Análisis Mutacional de ADN, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA::DNA Mutational Analysis [Medical Subject Headings], Triple-negative breast cancer, EGFR inhibitors, Cetuximab, Queratina-5, Marcadores biológicos de tumor, Proteínas ras, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Neoplasms, Basal Cell [Medical Subject Headings], Queratina-6, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunohistochemistry, Proteínas Proto-Oncogénicas, Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::Keratins::Keratins, Type II::Keratin-5 [Medical Subject Headings], ErbB Receptors, Gene Expression Regulation, Neoplastic, Oncology, Receptors, Estrogen, Neoplasias de la mama, Inhibidores de las Proteína Quinasas, Health Care::Health Services Administration::Patient Care Management::Patient Selection [Medical Subject Headings], Neoplasias vasocelulares, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Histocytochemistry::Immunohistochemistry [Medical Subject Headings], Female, KRAS, Chemicals and Drugs::Biological Factors::Biological Markers::Tumor Markers, Biological [Medical Subject Headings], Receptors, Progesterone, medicine.drug, Research Article, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], Receptores estrogénicos, Selección de pacientes, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone [Medical Subject Headings], Breast Neoplasms, Receptores de progesterona, Biology, lcsh:RC254-282, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [Medical Subject Headings], Proto-Oncogene Proteins p21(ras), EGFR protein, human, Breast cancer, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, Epidermal Growth Factor [Medical Subject Headings], Proto-Oncogene Proteins, medicine, Genetics, Biomarkers, Tumor, Panitumumab, Humans, Protein Kinase Inhibitors, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::Keratins::Keratins, Type II::Keratin-6 [Medical Subject Headings], Neoplasms, Basal Cell, Mutación, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Oncogene Proteins::Proto-Oncogene Proteins [Medical Subject Headings], Patient Selection, Keratin-6, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction [Medical Subject Headings], ERBB2 protein, human, medicine.disease, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Neoplastic [Medical Subject Headings], Receptor del Factor de Crecimiento Epidérmico, Check Tags::Female [Medical Subject Headings], Mutation, Reacción en Cadena de la Polimerasa, Cancer research, ras Proteins, Keratin-5, Regulación Neoplásica de la Expresión Génica, Inmunohistoquímica
Abstract

Background Mutational analysis of the KRAS gene has recently been established as a complementary in vitro diagnostic tool for the identification of patients with colorectal cancer who will not benefit from anti-epidermal growth factor receptor (EGFR) therapies. Assessment of the mutation status of KRAS might also be of potential relevance in other EGFR-overexpressing tumors, such as those occurring in breast cancer. Although KRAS is mutated in only a minor fraction of breast tumors (5%), about 60% of the basal-like subtype express EGFR and, therefore could be targeted by EGFR inhibitors. We aimed to study the mutation frequency of KRAS in that subtype of breast tumors to provide a molecular basis for the evaluation of anti-EGFR therapies. Methods Total, genomic DNA was obtained from a group of 35 formalin-fixed paraffin-embedded, triple-negative breast tumor samples. Among these, 77.1% (27/35) were defined as basal-like by immunostaining specific for the established surrogate markers cytokeratin (CK) 5/6 and/or EGFR. KRAS mutational status was determined in the purified DNA samples by Real Time (RT)-PCR using primers specific for the detection of wild-type KRAS or the following seven oncogenic somatic mutations: Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp. Results We found no evidence of KRAS oncogenic mutations in all analyzed tumors. Conclusions This study indicates that KRAS mutations are very infrequent in triple-negative breast tumors and that EGFR inhibitors may be of potential benefit in the treatment of basal-like breast tumors, which overexpress EGFR in about 60% of all cases.

Published
2009

46. Human pregnane X receptor is expressed in breast carcinomas, potential heterodimers formation between hPXR and RXR-alpha

Author

Isabel Conde, Julio Pérez, Benito Fraile, Ricardo Paniagua, Javier Zamora, Maria V.T. Lobo, Emilio Alba, Francisco González, María I. Arenas, Universidad de Alcalá. Departamento de Biología Celular y Genética, [Conde,I, Lobo,MVT, Pérez,J, Fraile,B, Paniagua,R, Arenas,MI] Department of Cell Biology and Genetics, University of Alcalá, Alcalá de Henares, Madrid, Spain. [Zamora,J] Clinical Biostatistics Unit, Hospital Ramón y Cajal, CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [González Sánchez,FJ, and Alba Conejo,E] Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Conde,I] Department of Cellular and Molecular Physiopathology, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain.

Subjects
Ciencia, SXR, Pathology, Receptors, Steroid, Cancer Research, Biología, Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings], Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Supervivencia sin Enfermedad, Receptores de Esteroides, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], pregnane X receptor, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Cytological Techniques::Histocytochemistry::Immunohistochemistry [Medical Subject Headings], Breast cancer, CIENCIA, Aged, 80 and over, Pregnane X receptor, Adulto, Neoplasia de la mama, Carcinoma, Ductal, Breast, Femenino, Pregnane X Receptor, SCIENCE, Middle Aged, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid [Medical Subject Headings], lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Carcinoma, Ductal::Carcinoma, Ductal, Breast [Medical Subject Headings], Immunohistochemistry, Humanos, Heterodimers, Human pregnane X receptor, Oncology, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Dimerization [Medical Subject Headings], Female, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Neoplasm Staging [Medical Subject Headings], Dimerization, Carcinoma in Situ, Research Article, Adult, medicine.medical_specialty, Western Blotting, Science, Anciano, Receptores x Retinoide, Blotting, Western, Breast Neoplasms, Retinoid X receptor, Steroid biosynthesis, Biology, Carcinoma in situ, lcsh:RC254-282, Disease-Free Survival, medicine, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Genetics, Dimerización, Humans, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Disease-Free Survival [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Neoplasm Staging, Receptor alfa X Retinoide, Mediana edad, Retinoid X Receptor alpha, Retinoid X receptor alpha, hPXR, medicine.disease, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma in Situ [Medical Subject Headings], Genética, Estadificación de Neoplasias, Anciano de 80 o más Años, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Retinoic Acid::Retinoid X Receptors [Medical Subject Headings], Retinoid X Receptors, Nuclear receptor, Check Tags::Female [Medical Subject Headings], Cancer cell, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Electrophoresis::Blotting, Western [Medical Subject Headings], Cancer research, Carcinoma ductal de mama, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Retinoic Acid::Retinoid X Receptors::Retinoid X Receptor alpha [Medical Subject Headings], Inmunohistoquímica
Abstract

14 p.-5 fig.-5 tab., [Background] The human pregnane X receptor (hPXR) is an orphan nuclear receptor that induces transcription of response elements present in steroid-inducible cytochrome P-450 gene promoters. This activation requires the participation of retinoid X receptors (RXRs), needed partners of hPXR to form heterodimers. We have investigated the expression of hPXR and RXRs in normal, premalignant, and malignant breast tissues, in order to determine whether their expression profile in localized infiltrative breast cancer is associated with an increased risk of recurrent disease., [Methods] Breast samples from 99 patients including benign breast diseases, in situ and infiltrative carcinomas were processed for immunohistochemistry and Western-blot analysis., [Results] Cancer cells from patients that developed recurrent disease showed a high cytoplasmic location of both hPXR isoforms. Only the infiltrative carcinomas that relapsed before 48 months showed nuclear location of hPXR isoform 2. This location was associated with the nuclear immunoexpression of RXR-alpha., [Conclusions] Breast cancer cells can express both variants 1 and 2 of hPXR. Infiltrative carcinomas that recurred showed a nuclear location of both hPXR and RXR-alpha; therefore, the overexpression and the subcellular location changes of hPXR could be considered as a potential new prognostic indicator.

Published
2008
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47. Retreatment with trastuzumab in Her2-positive metastatic breast cancer patients: a clinical study

Author

F Carabantes-Ocón, A Casaus-Hazañas, S Luna, L Burgos-Garcia, E Villar-Chamorro, E Saez-Lara, C Martínez, [Carabante-Ocón,F, Saez-Lara, E, Burgos-Garcia, L, Villar-Chamorro, E, Casaus-Hazañas, A, Luna, S, and Martínez, C] Unidad de Mama, Hospital Carlos Haya, Málaga, Spain.

Subjects
Oncology, medicine.medical_specialty, MBC, business.industry, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Retreatment [Medical Subject Headings], neoplasias de la mama, chemotherapies, medicine.disease, Metastatic breast cancer, Clinical study, trastuzumab, Breast cancer, Surgical oncology, Trastuzumab, Internal medicine, medicine, Retratamiento, her2-positive, business, skin and connective tissue diseases, neoplasms, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], medicine.drug
Abstract

Objective: To study the benefit of trastuzumab in monotherapy or combined with different chemotherapeutic agents in the treatment for Her2+ metastatic breast cancer (MBC) patients after progression on prior trastuzumab therapy. Yes

Published
2007

48. Study of the combination gemcitabine and trastuzumab in the treatment of HER2+ metastatic breast cancer

Author

E González-Jiménez, MJ Titos, R Olivencia-Dueso, S Menjón-Beltrán, [Menjón-Beltrán,S, Olivencia-Dueso,R, González-Jiménez,E, and Titos,MJ] Unidad de Ginecología Oncológica, Hospital Universitario Virgen de las Nieves, Granada, Spain.

Subjects
Oncology, medicine.medical_specialty, education, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, erbB-2 [Medical Subject Headings], Breast cancer, Stable Disease, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized [Medical Subject Headings], Surgical oncology, Trastuzumab, Internal medicine, parasitic diseases, Diseases::Neoplasms::Neoplastic Processes::Neoplasm Metastasis [Medical Subject Headings], medicine, Receptor erbB-2, skin and connective tissue diseases, neoplasms, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], business.industry, Metástasis de la Neoplasia, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [Medical Subject Headings], Neoplasias de la Mama, Femenino, medicine.disease, Anticuerpos Monoclonales Humanizados, Antineoplásicos, Metastatic breast cancer, Gemcitabine, Humanos, Antimetabolitos Antineoplásicos, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Antimetabolites::Antimetabolites, Antineoplastic [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], sense organs, business, geographic locations, medicine.drug
Abstract

Poster Presentation. This article is part of the supplement: VII Madrid Breast Cancer Conference: Changes in the treatment of breast cancer. Trastuzumab and gemcitabine are two active drugs for meta-static breast cancer (MBC) treatment. We conducted a retrospective study of this combination in patients with Her2+ MBC in our hospital. Yes

Published
2007

49. Clinical role of trastuzumab in metastatic breast cancer: experience of a center

Author

E Gonzalez, R Olivencia, S Menjón-Beltrán, [Menjón-Beltrán,S, Olivencia,R, and Gonzalez,E] Unidad de Ginecología Oncológica, Hospital Universitario Virgen de las Nieves, Granada, Spain

Subjects
Oncology, medicine.medical_specialty, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, erbB-2 [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Breast cancer, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized [Medical Subject Headings], Trastuzumab, Internal medicine, Diseases::Neoplasms::Neoplastic Processes::Neoplasm Metastasis [Medical Subject Headings], parasitic diseases, medicine, Center (algebra and category theory), Receptor erbB-2, skin and connective tissue diseases, neoplasms, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], business.industry, Metástasis de la Neoplasia, Neoplasias de la Mama, Femenino, Anticuerpos Monoclonales Humanizados, medicine.disease, Metastatic breast cancer, Humanos, Check Tags::Female [Medical Subject Headings], sense organs, business, geographic locations, medicine.drug
Abstract

This article is part of the supplement: VII Madrid Breast Cancer Conference: Changes in the treatment of breast cancer Objective: To study the efficacy of different regimens of treatment based on trastuzumab in patients with Her2+ metastatic breast cancer (MBC). Yes

Published
2007
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50. Telehealth system (e-CUIDATE) to improve quality of life in breast cancer survivors: rationale and study protocol for a randomized clinical trial

Author

Irene Cantarero-Villanueva, Noelia Galiano-Castillo, Carolina Fernández-Lao, Marta Legerén-Alvarez, Lourdes Díaz-Rodríguez, Angelica Ariza-García, Rosario Del-Moral-Ávila, Manuel Arroyo-Morales, Carmen Sánchez-Salado, [Galiano-Castillo,N, Ariza-García,A, Cantarero-Villnueva,I, Fernández-Lao,L, Arroyo-Morales,M] Department Physical Therapy, University of Granada, Spain. [Ariza-García,A] Physical Medicine and Rehabilitation Department, Clinico Universitario San Cecilio Hospital, Andalusian Health Service, Granada, Spain. [Díaz-Rodríguez,L] Nursing Department, University of Granada, Spain. [Legerén-Álvarez,M] Medical Oncology Unit, Clinico Universitario San Cecilio Hospital, Andalusian Health Service, Granada, Spain. [Sánchez-Salado,C] Breast Oncology Unit, Hospital Virgen de las Nieves, Granada, Spain. [Moral-Avila,R del] Radiotherapy Oncology Unit, Hospital Virgen de las Nieves, Granada, Spain., and The study was funded by a research project grant (FIS PI10/02749-02764) from the Health Institute Carlos III and PN I+D+I 2008–2011 (FEDER funds), a grant (Program FPU AP2010-6075) from Education Ministry, Madrid, Spanish Government and a grant of Andalusian Health Service, Junta de Andalucia (PI-0457-2010).

Subjects
Research design, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Feasibility Studies [Medical Subject Headings], Time Factors, Calidad de vida, Phenomena and Processes::Physical Phenomena::Time::Time Factors [Medical Subject Headings], España, Physical fitness, Medicine (miscellaneous), Named Groups::Persons::Survivors [Medical Subject Headings], Hospital Anxiety and Depression Scale, law.invention, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination [Medical Subject Headings], Study Protocol, Clinical Protocols, Randomized controlled trial, Quality of life, law, Surveys and Questionnaires, Terapia asistida por computador, Telerehabilitation, Pharmacology (medical), Survivors, Breast, Information Science::Information Science::Medical Informatics::Medical Informatics Applications::Decision Making, Computer-Assisted::Therapy, Computer-Assisted [Medical Subject Headings], Pain Measurement, Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Ergometry::Exercise Test [Medical Subject Headings], Disciplines and Occupations::Natural Science Disciplines::Science::Research::Research Design [Medical Subject Headings], Telemedicine, Exercise Therapy, Treatment Outcome, Research Design, Terapia por ejercicio, Information Science::Information Science::Computing Methodologies::Computer Systems::Computer Communication Networks::Internet [Medical Subject Headings], Female, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Neoplasm Staging [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Physical Therapy Modalities::Exercise Therapy [Medical Subject Headings], medicine.medical_specialty, Visual analogue scale, Breast Neoplasms, Disciplines and Occupations::Human Activities::Physical Fitness [Medical Subject Headings], Information Science::Information Science::Data Collection::Questionnaires [Medical Subject Headings], Sobrevivientes, Information Science::Information Science::Communications Media::Telecommunications::Telemedicine [Medical Subject Headings], Valor predictivo de las pruebas, Breast cancer, Predictive Value of Tests, Disciplines and Occupations::Social Sciences::Quality of Life [Medical Subject Headings], Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Outcome and Process Assessment (Health Care)::Outcome Assessment (Health Care)::Treatment Outcome [Medical Subject Headings], medicine, Humans, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Research Design::Sensitivity and Specificity::Predictive Value of Tests [Medical Subject Headings], Physical Examination, Exercise, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Neoplasm Staging, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Neurological::Neurologic Examination::Pain Measurement [Medical Subject Headings], Internet, Proyectos de investigación, business.industry, medicine.disease, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Clinical Protocols [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Risk Reduction Behavior [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Physical Fitness, Spain, Therapy, Computer-Assisted, Exercise Test, Quality of Life, Physical therapy, Feasibility Studies, Neoplasm, business, Risk Reduction Behavior
Abstract

Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; BACKGROUND Breast cancer survivors suffer physical impairment after oncology treatment. This impairment reduces quality of life (QoL) and increase the prevalence of handicaps associated to unhealthy lifestyle (for example, decreased aerobic capacity and strength, weight gain, and fatigue). Recent work has shown that exercise adapted to individual characteristics of patients is related to improved overall and disease-free survival. Nowadays, technological support using telerehabilitation systems is a promising strategy with great advantage of a quick and efficient contact with the health professional. It is not known the role of telerehabilitation through therapeutic exercise as a support tool to implement an active lifestyle which has been shown as an effective resource to improve fitness and reduce musculoskeletal disorders of these women. METHODS / DESIGN This study will use a two-arm, assessor blinded, parallel randomized controlled trial design. People will be eligible if: their diagnosis is of stages I, II, or IIIA breast cancer; they are without chronic disease or orthopedic issues that would interfere with ability to participate in a physical activity program; they had access to the Internet and basic knowledge of computer use or living with a relative who has this knowledge; they had completed adjuvant therapy except for hormone therapy and not have a history of cancer recurrence; and they have an interest in improving lifestyle. Participants will be randomized into e-CUIDATE or usual care groups. E-CUIDATE give participants access to a range of contents: planning exercise arranged in series with breathing exercises, mobility, strength, and stretching. All of these exercises will be assigned to women in the telerehabilitation group according to perceived needs. The control group will be asked to maintain their usual routine. Study endpoints will be assessed after 8 weeks (immediate effects) and after 6 months. The primary outcome will be QoL measured by The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 version 3.0 and breast module called The European Organization for Research and Treatment of Cancer Breast Cancer-Specific Quality of Life questionnaire. The secondary outcomes: pain (algometry, Visual Analogue Scale, Brief Pain Inventory short form); body composition; physical measurement (abdominal test, handgrip strength, back muscle strength, and multiple sit-to-stand test); cardiorespiratory fitness (International Fitness Scale, 6-minute walk test, International Physical Activity Questionnaire-Short Form); fatigue (Piper Fatigue Scale and Borg Fatigue Scale); anxiety and depression (Hospital Anxiety and Depression Scale); cognitive function (Trail Making Test and Auditory Consonant Trigram); accelerometry; lymphedema; and anthropometric perimeters. DISCUSSION This study investigates the feasibility and effectiveness of a telerehabilitation system during adjuvant treatment of patients with breast cancer. If this treatment option is effective, telehealth systems could offer a choice of supportive care to cancer patients during the survivorship phase. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01801527. Yes

Published
2013
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