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2,612 results on '"Godwin, Andrew"'

2. Clinical and biomarker results from a phase II trial of combined cabozantinib and durvalumab in patients with chemotherapy-refractory colorectal cancer (CRC): CAMILLA CRC cohort

Author

Saeed, Anwaar, Park, Robin, Pathak, Harsh, Al-Bzour, Ayah Nedal, Dai, Junqiang, Phadnis, Milind, Al-Rajabi, Raed, Kasi, Anup, Baranda, Joaquina, Sun, Weijing, Williamson, Stephen, Chiu, Yu-Chiao, Osmanbeyoglu, Hatice Ulku, Madan, Rashna, Abushukair, Hassan, Mulvaney, Kelly, Godwin, Andrew K., and Saeed, Azhar

Published
2024
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3. An Integrated Approach to Protein Discovery and Detection From Complex Biofluids.

Author

Luu, Gordon, Ge, Chang, Tang, Yisha, Li, Kailiang, Cologna, Stephanie, Godwin, Andrew, Burdette, Joanna, Su, Judith, and Sanchez, Laura

Subjects
biomarkers, mass spectrometry, murine model, optical resonators, ovarian cancer, Humans, Animals, Female, Cystatin A, Early Detection of Cancer, Ovarian Neoplasms
Abstract

Ovarian cancer, a leading cause of cancer-related deaths among women, has been notoriously difficult to screen for and diagnose early, as early detection significantly improves survival. Researchers and clinicians seek routinely usable and noninvasive screening methods; however, available methods (i.e., biomarker screening) lack desirable sensitivity/specificity. The most fatal form, high-grade serous ovarian cancer, often originate in the fallopian tube; therefore, sampling from the vaginal environment provides more proximal sources for tumor detection. To address these shortcomings and leverage proximal sampling, we developed an untargeted mass spectrometry microprotein profiling method and identified cystatin A, which was validated in an animal model. To overcome the limits of detection inherent to mass spectrometry, we demonstrated that cystatin A is present at 100 pM concentrations using a label-free microtoroid resonator and translated our workflow to patient-derived clinical samples, highlighting the potential utility of early stage detection where biomarker levels would be low.

Published
2023

4. Ovarian cancer pathology characteristics as predictors of variant pathogenicity in BRCA1 and BRCA2

Author

O’Mahony, Denise G, Ramus, Susan J, Southey, Melissa C, Meagher, Nicola S, Hadjisavvas, Andreas, John, Esther M, Hamann, Ute, Imyanitov, Evgeny N, Andrulis, Irene L, Sharma, Priyanka, Daly, Mary B, Hake, Christopher R, Weitzel, Jeffrey N, Jakubowska, Anna, Godwin, Andrew K, Arason, Adalgeir, Bane, Anita, Simard, Jacques, Soucy, Penny, Caligo, Maria A, Mai, Phuong L, Claes, Kathleen BM, Teixeira, Manuel R, Chung, Wendy K, Lazaro, Conxi, Hulick, Peter J, Toland, Amanda E, Pedersen, Inge Sokilde, Neuhausen, Susan L, Vega, Ana, de la Hoya, Miguel, Nevanlinna, Heli, Dhawan, Mallika, Zampiga, Valentina, Danesi, Rita, Varesco, Liliana, Gismondi, Viviana, Vellone, Valerio Gaetano, James, Paul A, Janavicius, Ramunas, Nikitina-Zake, Liene, Nielsen, Finn Cilius, van Overeem Hansen, Thomas, Pejovic, Tanja, Borg, Ake, Rantala, Johanna, Offit, Kenneth, Montagna, Marco, Nathanson, Katherine L, Domchek, Susan M, Osorio, Ana, García, María J, Karlan, Beth Y, De Fazio, Anna, Bowtell, David, McGuffog, Lesley, Leslie, Goska, Parsons, Michael T, Dörk, Thilo, Speith, Lisa-Marie, dos Santos, Elizabeth Santana, da Costa, Alexandre André BA, Radice, Paolo, Peterlongo, Paolo, Papi, Laura, Engel, Christoph, Hahnen, Eric, Schmutzler, Rita K, Wappenschmidt, Barbara, Easton, Douglas F, Tischkowitz, Marc, Singer, Christian F, Tan, Yen Yen, Whittemore, Alice S, Sieh, Weiva, Brenton, James D, Yannoukakos, Drakoulis, Fostira, Florentia, Konstantopoulou, Irene, Soukupova, Jana, Vocka, Michal, Chenevix-Trench, Georgia, Pharoah, Paul DP, Antoniou, Antonis C, Goldgar, David E, Spurdle, Amanda B, and Michailidou, Kyriaki

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Cancer, Breast Cancer, Genetics, Ovarian Cancer, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Humans, Female, Virulence, BRCA1 Protein, BRCA2 Protein, Ovarian Neoplasms, Genetic Predisposition to Disease, Breast Neoplasms, HEBON Investigators, GEMO Study Collaborators, AOCS Group, CZECANCA Consortium, Consortium of Investigators of Modifiers of BRCA1/2, Evidence-based Network for the Interpretation of Germline Mutant Alleles Consortium, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundThe distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system.MethodsData for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, with BRCA1 and BRCA2 variant pathogenicity. Estimates were aligned to ACMG/AMP code strengths (supporting, moderate, strong).ResultsNo histological subtype provided informative ACMG/AMP evidence in favour of BRCA1 and BRCA2 variant pathogenicity. Evidence against variant pathogenicity was estimated for the mucinous and clear cell histologies (supporting) and borderline cases (moderate). Refined associations are provided according to tumour grade, invasion and age at diagnosis.ConclusionsWe provide detailed estimates for predicting BRCA1 and BRCA2 variant pathogenicity based on ovarian tumour characteristics. This evidence can be combined with other variant information under the ACMG/AMP classification system, to improve classification and carrier clinical management.

Published
2023

6. Thymidine kinase activity levels in serum can identify HR+ metastatic breast cancer patients with a low risk of early progression (SWOG S0226)

Author

Bergqvist, Mattias, Nordmark, Adrian, Williams, Amy, Paoletti, Costanza, Barlow, William, Cobain, Erin F, Mehta, Rita S, Gralow, Julie R, Hortobagyi, Gabriel N, Albain, Kathy S, Pusztai, Lajos, Sharma, Priyanka, Godwin, Andrew K, Thompson, Alastair M, Hayes, Daniel F, and Rae, James M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Prevention, Cancer, Breast Cancer, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Female, Humans, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Breast Neoplasms, Prognosis, Progression-Free Survival, Receptor, ErbB-2, Thymidine Kinase, Thymidine kinase, biomarker, disease progression, monitoring treatment, breast cancer, endocrine therapy, Receptor, erbB-2, Environmental Biotechnology, Toxicology, Bioinformatics and computational biology, Medical biotechnology, Environmental biotechnology
Abstract

BackgroundSome patients with metastatic breast cancer (MBC) stay on endocrine therapy (ET) for years and others progress quickly. Serum thymidine kinase activity (TKa), an indicator of cell-proliferation, is a potential biomarker for monitoring ET and predicting MBC outcome. We have previously reported TKa as being prognostic in MBC in SWOG S0226. Here, new data on progression within 30/60 days post sampling, with a new, FDA approved version of DiviTum®TKa highlighting differences vs. a Research Use Only version is reported.Methods1,546 serum samples from 454 patients were assessed, collected at baseline and at 4 subsequent timepoints during treatment. A new predefined cut-off tested the ability to predict disease progression. A new measuring unit, DuA (DiviTum® unit of Activity) is adopted.ResultsA DiviTum®TKa score

Published
2023

8. Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

Author

Hakkaart, Christopher, Pearson, John F, Marquart, Louise, Dennis, Joe, Wiggins, George AR, Barnes, Daniel R, Robinson, Bridget A, Mace, Peter D, Aittomäki, Kristiina, Andrulis, Irene L, Arun, Banu K, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Belhadj, Sami, Berger, Lieke, Blok, Marinus J, Boonen, Susanne E, Borde, Julika, Bradbury, Angela R, Brunet, Joan, Buys, Saundra S, Caligo, Maria A, Campbell, Ian, Chung, Wendy K, Claes, Kathleen BM, Collonge-Rame, Marie-Agnès, Cook, Jackie, Cosgrove, Casey, Couch, Fergus J, Daly, Mary B, Dandiker, Sita, Davidson, Rosemarie, de la Hoya, Miguel, de Putter, Robin, Delnatte, Capucine, Dhawan, Mallika, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M, Donaldson, Alan, Eason, Jacqueline, Easton, Douglas F, Ehrencrona, Hans, Engel, Christoph, Evans, D Gareth, Faust, Ulrike, Feliubadaló, Lidia, Fostira, Florentia, Friedman, Eitan, Frone, Megan, Frost, Debra, Garber, Judy, Gayther, Simon A, Gehrig, Andrea, Gesta, Paul, Godwin, Andrew K, Goldgar, David E, Greene, Mark H, Hahnen, Eric, Hake, Christopher R, Hamann, Ute, Hansen, Thomas VO, Hauke, Jan, Hentschel, Julia, Herold, Natalie, Honisch, Ellen, Hulick, Peter J, Imyanitov, Evgeny N, Isaacs, Claudine, Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, James, Paul A, Janavicius, Ramunas, John, Esther M, Joseph, Vijai, Karlan, Beth Y, Kemp, Zoe, Kirk, Judy, Konstantopoulou, Irene, Koudijs, Marco, Kwong, Ava, Laitman, Yael, Lalloo, Fiona, Lasset, Christine, Lautrup, Charlotte, Lazaro, Conxi, Legrand, Clémentine, Leslie, Goska, Lesueur, Fabienne, Mai, Phuong L, Manoukian, Siranoush, Mari, Véronique, Martens, John WM, McGuffog, Lesley, Mebirouk, Noura, Meindl, Alfons, Miller, Austin, and Montagna, Marco

Subjects
Human Genome, Prevention, Breast Cancer, Cancer, Genetics, Aetiology, 2.1 Biological and endogenous factors, BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, DNA Copy Number Variations, Female, Genetic Predisposition to Disease, Heterozygote, Humans, RNA, Messenger, GEMO Study Collaborators, EMBRACE Collaborators, SWE-BRCA Investigators, kConFab Investigators, HEBON Investigators
Abstract

The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.

Published
2022

11. Image analysis-based tumor infiltrating lymphocytes measurement predicts breast cancer pathologic complete response in SWOG S0800 neoadjuvant chemotherapy trial

Author

Fanucci, Kristina A., Bai, Yalai, Pelekanou, Vasiliki, Nahleh, Zeina A., Shafi, Saba, Burela, Sneha, Barlow, William E., Sharma, Priyanka, Thompson, Alastair M., Godwin, Andrew K., Rimm, David L., Hortobagyi, Gabriel N., Liu, Yihan, Wang, Leona, Wei, Wei, Pusztai, Lajos, and Blenman, Kim R. M.

Published
2023
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13. A window of opportunity trial evaluating intratumoral injection of Copaxone® in patients with percutaneously accessible tumors

Author

Baranda, Joaquina C., Mohyuddin, Ghulam Rehman, Bur, Andrés M., Shnayder, Yelizaveta, Sweeney, Kyle R., Kakarala, Kiran, Prouty, Megan, Pathak, Harsh, Puri, Rajni, Mitra, Amrita, Madan, Rashna, Forrest, M. Laird, Huang, Aric, Weir, Scott, Godwin, Andrew K., Alhakamy, Nabil A., Griffin, J. Daniel, and Berkland, Cory J.

Published
2023
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14. Correction: Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author

Dareng, Eileen O, Tyrer, Jonathan P, Barnes, Daniel R, Jones, Michelle R, Yang, Xin, Aben, Katja KH, Adank, Muriel A, Agata, Simona, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Aravantinos, Gerasimos, Arun, Banu K, Augustinsson, Annelie, Balmaña, Judith, Bandera, Elisa V, Barkardottir, Rosa B, Barrowdale, Daniel, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q, Bjorge, Line, Black, Amanda, Bogdanova, Natalia V, Bonanni, Bernardo, Borg, Ake, Brenton, James D, Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S, Cai, Hui, Caligo, Maria A, Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J, Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K, Claes, Kathleen BM, Colonna, Sarah, Cook, Linda S, Couch, Fergus J, Daly, Mary B, Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A, Domchek, Susan M, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana M, Eliassen, Heather A, Engel, Christoph, Evans, Gareth D, Fasching, Peter A, Flanagan, James M, Fortner, Renée T, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A, Garber, Judy, Gensini, Francesca, Giles, Graham G, Glendon, Gord, Godwin, Andrew K, Goodman, Marc T, Greene, Mark H, Gronwald, Jacek, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hamann, Ute, Hansen, Thomas VO, Harris, Holly R, Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle AT, Høgdall, Estrid, Høgdall, Claus K, Hopper, John L, Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J, Huntsman, David G, Imyanitov, Evgeny N, Isaacs, Claudine, Jakubowska, Anna, James, Paul A, and Janavicius, Ramunas

Subjects
GEMO Study Collaborators, GC-HBOC Study Collaborators, EMBRACE Collaborators, OPAL Study Group, AOCS Group, KConFab Investigators, HEBON Investigators, OCAC Consortium, CIMBA Consortium, Genetics, Clinical Sciences, Genetics & Heredity
Published
2022

15. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author

Dareng, Eileen O, Tyrer, Jonathan P, Barnes, Daniel R, Jones, Michelle R, Yang, Xin, Aben, Katja KH, Adank, Muriel A, Agata, Simona, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Aravantinos, Gerasimos, Arun, Banu K, Augustinsson, Annelie, Balmaña, Judith, Bandera, Elisa V, Barkardottir, Rosa B, Barrowdale, Daniel, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q, Bjorge, Line, Black, Amanda, Bogdanova, Natalia V, Bonanni, Bernardo, Borg, Ake, Brenton, James D, Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S, Cai, Hui, Caligo, Maria A, Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J, Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K, Claes, Kathleen BM, Colonna, Sarah, Cook, Linda S, Couch, Fergus J, Daly, Mary B, Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A, Domchek, Susan M, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana M, Eliassen, Heather A, Engel, Christoph, Evans, Gareth D, Fasching, Peter A, Flanagan, James M, Fortner, Renée T, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A, Garber, Judy, Gensini, Francesca, Giles, Graham G, Glendon, Gord, Godwin, Andrew K, Goodman, Marc T, Greene, Mark H, Gronwald, Jacek, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hamann, Ute, Hansen, Thomas VO, Harris, Holly R, Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle AT, Høgdall, Estrid, Høgdall, Claus K, Hopper, John L, Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J, Huntsman, David G, Imyanitov, Evgeny N, Isaacs, Claudine, Jakubowska, Anna, James, Paul A, and Janavicius, Ramunas

Subjects
Prevention, Cancer, Ovarian Cancer, Rare Diseases, Good Health and Well Being, Bayes Theorem, Breast Neoplasms, Carcinoma, Ovarian Epithelial, Female, Genetic Predisposition to Disease, Humans, Male, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, GEMO Study Collaborators, GC-HBOC Study Collaborators, EMBRACE Collaborators, OPAL Study Group, AOCS Group, KConFab Investigators, HEBON Investigators, OCAC Consortium, CIMBA Consortium, Genetics, Clinical Sciences, Genetics & Heredity
Abstract

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.

Published
2022

17. Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients.

Author

Yau, Christina, Osdoit, Marie, van der Noordaa, Marieke, Shad, Sonal, Wei, Jane, de Croze, Diane, Hamy, Anne-Sophie, Laé, Marick, Reyal, Fabien, Sonke, Gabe S, Steenbruggen, Tessa G, van Seijen, Maartje, Wesseling, Jelle, Martín, Miguel, Del Monte-Millán, Maria, López-Tarruella, Sara, I-SPY 2 Trial Consortium, Boughey, Judy C, Goetz, Matthew P, Hoskin, Tanya, Gould, Rebekah, Valero, Vicente, Edge, Stephen B, Abraham, Jean E, Bartlett, John MS, Caldas, Carlos, Dunn, Janet, Earl, Helena, Hayward, Larry, Hiller, Louise, Provenzano, Elena, Sammut, Stephen-John, Thomas, Jeremy S, Cameron, David, Graham, Ashley, Hall, Peter, Mackintosh, Lorna, Fan, Fang, Godwin, Andrew K, Schwensen, Kelsey, Sharma, Priyanka, DeMichele, Angela M, Cole, Kimberly, Pusztai, Lajos, Kim, Mi-Ok, van 't Veer, Laura J, Esserman, Laura J, and Symmans, W Fraser

Subjects
I-SPY 2 Trial Consortium, Humans, Breast Neoplasms, Neoplasm, Residual, Receptor, erbB-2, Chemotherapy, Adjuvant, Neoadjuvant Therapy, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Young Adult, Receptor, ErbB-2, Breast Cancer, Patient Safety, Clinical Research, Cancer, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundPrevious studies have independently validated the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. We used results from several independent cohorts in a pooled patient-level analysis to evaluate the relationship of RCB with long-term prognosis across different phenotypic subtypes of breast cancer, to assess generalisability in a broad range of practice settings.MethodsIn this pooled analysis, 12 institutes and trials in Europe and the USA were identified by personal communications with site investigators. We obtained participant-level RCB results, and data on clinical and pathological stage, tumour subtype and grade, and treatment and follow-up in November, 2019, from patients (aged ≥18 years) with primary stage I-III breast cancer treated with neoadjuvant chemotherapy followed by surgery. We assessed the association between the continuous RCB score and the primary study outcome, event-free survival, using mixed-effects Cox models with the incorporation of random RCB and cohort effects to account for between-study heterogeneity, and stratification to account for differences in baseline hazard across cancer subtypes defined by hormone receptor status and HER2 status. The association was further evaluated within each breast cancer subtype in multivariable analyses incorporating random RCB and cohort effects and adjustments for age and pretreatment clinical T category, nodal status, and tumour grade. Kaplan-Meier estimates of event-free survival at 3, 5, and 10 years were computed for each RCB class within each subtype.FindingsWe analysed participant-level data from 5161 patients treated with neoadjuvant chemotherapy between Sept 12, 1994, and Feb 11, 2019. Median age was 49 years (IQR 20-80). 1164 event-free survival events occurred during follow-up (median follow-up 56 months [IQR 0-186]). RCB score was prognostic within each breast cancer subtype, with higher RCB score significantly associated with worse event-free survival. The univariable hazard ratio (HR) associated with one unit increase in RCB ranged from 1·55 (95% CI 1·41-1·71) for hormone receptor-positive, HER2-negative patients to 2·16 (1·79-2·61) for the hormone receptor-negative, HER2-positive group (with or without HER2-targeted therapy; p

Published
2022

18. Evaluating Serum Thymidine Kinase 1 in Hormone Receptor Positive Metastatic Breast Cancer Patients Receiving First Line Endocrine Therapy in the SWOG S0226 Trial

Author

Paoletti, Costanza, Barlow, William E, Cobain, Erin F, Bergqvist, Mattias, Mehta, Rita S, Gralow, Julie R, Hortobagyi, Gabriel N, Albain, Kathy S, Pusztai, Lajos, Sharma, Priyanka, Godwin, Andrew K, Thompson, Alastair M, Hayes, Daniel F, and Rae, James M

Subjects
Clinical Research, Cancer, Breast Cancer, Rehabilitation, Clinical Trials and Supportive Activities, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Hormonal, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Clinical Trials as Topic, Female, Humans, Kaplan-Meier Estimate, Middle Aged, Prognosis, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Retrospective Studies, Thymidine Kinase, Treatment Outcome, Receptor, erbB-2, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeSerum thymidine kinase 1 (sTK1) activity is associated with poor prognosis in metastatic breast cancer (MBC). We assessed the prognostic effect of sTK1 in patients with hormone receptor-positive MBC treated on a prospective randomized trial of anastrozole (A) versus A plus fulvestrant (A + F).Patients and methodssTK1 was assessed in 1,726 serums [baseline (BL), cycles 2, 3, 4, and 7] using the DiviTum assay. A prespecified cutoff of ≥200 Du/L was considered high. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier, log-rank tests, and Cox regression.ResultsBL sTK1 was elevated in 171 (40%) of 432 patients. Patients with high versus low BL sTK1 had significantly worse PFS [median 11.2 vs. 17.3 months, HR = 1.76; 95% confidence interval (CI; 1.43-2.16); P < 0.0001] and OS [median 30 vs. 58 months, HR = 2.38; 95% CI (1.91-2.98); P < 0.0001]. OS was significantly better for patients with high sTK1 who did not have prior adjuvant tamoxifen and who received A + F versus A alone [median 46 vs. 21 months, HR = 0.58; 95% CI (0.38-0.87); P = 0.0087]. Patients with low sTK1 had no difference in outcomes by therapy (P = 0.44). At serial timepoints, high versus low sTK1 had significantly worse subsequent PFS and OS [at cycle 2: PFS HR = 1.70, 95% CI (1.34-2.17); P < 0.0001, OS HR = 2.51, 95% CI (1.93-3.26); P < 0.0001].ConclusionsHigh sTK1 at BL and subsequent timepoints is associated with worse prognosis in patients with MBC starting first-line endocrine therapy (ET). Patients with low sTK1 at BL have comparable outcomes on single-agent or combination ET.

Published
2021

19. The predictive ability of the 313 variant-based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant.

Author

Lakeman, Inge MM, van den Broek, Alexandra J, Vos, Juliën AM, Barnes, Daniel R, Adlard, Julian, Andrulis, Irene L, Arason, Adalgeir, Arnold, Norbert, Arun, Banu K, Balmaña, Judith, Barrowdale, Daniel, Benitez, Javier, Borg, Ake, Caldés, Trinidad, Caligo, Maria A, Chung, Wendy K, Claes, Kathleen BM, GEMO Study Collaborators, EMBRACE Collaborators, Collée, J Margriet, Couch, Fergus J, Daly, Mary B, Dennis, Joe, Dhawan, Mallika, Domchek, Susan M, Eeles, Ros, Engel, Christoph, Evans, D Gareth, Feliubadaló, Lidia, Foretova, Lenka, Friedman, Eitan, Frost, Debra, Ganz, Patricia A, Garber, Judy, Gayther, Simon A, Gerdes, Anne-Marie, Godwin, Andrew K, Goldgar, David E, Hahnen, Eric, Hake, Christopher R, Hamann, Ute, Hogervorst, Frans BL, Hooning, Maartje J, Hopper, John L, Hulick, Peter J, Imyanitov, Evgeny N, OCGN Investigators, HEBON Investigators, KconFab Investigators, Isaacs, Claudine, Izatt, Louise, Jakubowska, Anna, James, Paul A, Janavicius, Ramunas, Jensen, Uffe Birk, Jiao, Yue, John, Esther M, Joseph, Vijai, Karlan, Beth Y, Kets, Carolien M, Konstantopoulou, Irene, Kwong, Ava, Legrand, Clémentine, Leslie, Goska, Lesueur, Fabienne, Loud, Jennifer T, Lubiński, Jan, Manoukian, Siranoush, McGuffog, Lesley, Miller, Austin, Gomes, Denise Molina, Montagna, Marco, Mouret-Fourme, Emmanuelle, Nathanson, Katherine L, Neuhausen, Susan L, Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Olah, Edith, Olopade, Olufunmilayo I, Park, Sue K, Parsons, Michael T, Peterlongo, Paolo, Piedmonte, Marion, Radice, Paolo, Rantala, Johanna, Rennert, Gad, Risch, Harvey A, Schmutzler, Rita K, Sharma, Priyanka, Simard, Jacques, Singer, Christian F, Stadler, Zsofia, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R, Teo, Soo Hwang, Teulé, Alex, Thomassen, Mads, and Thull, Darcy L

Subjects
GEMO Study Collaborators, EMBRACE Collaborators, OCGN Investigators, HEBON Investigators, KconFab Investigators, Humans, Breast Neoplasms, Genetic Predisposition to Disease, BRCA1 Protein, BRCA2 Protein, Risk Factors, Retrospective Studies, Heterozygote, Mutation, Adult, Female, Prevention, Cancer, Aging, Breast Cancer, 2.1 Biological and endogenous factors, Genetics & Heredity, Genetics, Clinical Sciences
Abstract

PurposeTo evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes.MethodsWe included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk.ResultsFor BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC

Published
2021

23. Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Author

Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A, Dennis, Joe, Tyrer, Jonathan P, Barnes, Daniel R, McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K, Adank, Muriel A, Agata, Simona, Ahearn, Thomas, Aittomäki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J, Arun, Banu K, Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Białkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E, Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S, Caldés, Trinidad, Caligo, Maria A, Campa, Daniele, Carter, Brian D, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Chung, Wendy K, Claes, Kathleen BM, Clarke, Christine L, GEMO Study Collaborators, EMBRACE Collaborators, Collée, J Margriet, Conroy, Don M, Czene, Kamila, Daly, Mary B, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M, Dörk, Thilo, Dos-Santos-Silva, Isabel, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Eliassen, A Heather, Engel, Christoph, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M, Garber, Judy, Garcia-Barberan, Vanesa, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, Gayther, Simon A, Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Greene, Mark H, Guénel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A, Hart, Steven N, He, Wei, Hogervorst, Frans BL, Hollestelle, Antoinette, and Hopper, John L

Subjects
GEMO Study Collaborators, EMBRACE Collaborators, KConFab Investigators, HEBON Investigators, ABCTB Investigators, Cancer
Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4.

Published
2021

24. Proteogenomic insights suggest druggable pathways in endometrial carcinoma

Author

Antczak, Andrzej, Anurag, Meenakshi, Bauer, Thomas, Birger, Chet, Birrer, Michael J., Borucki, Melissa, Cai, Shuang, Calinawan, Anna, Carr, Steven A., Castro, Patricia, Cerda, Sandra, Chan, Daniel W., Chesla, David, Cieslik, Marcin P., Cottingham, Sandra, Dhir, Rajiv, Domagalski, Marcin J., Druker, Brian J., Duffy, Elizabeth, Edwards, Nathan J., Edwards, Robert, Ellis, Matthew J., Eschbacher, Jennifer, Fam, Mina, Fevrier-Sullivan, Brenda, Francis, Jesse, Freymann, John, Gabriel, Stacey, Getz, Gad, Gillette, Michael A., Godwin, Andrew K., Goldthwaite, Charles A., Grady, Pamela, Hafron, Jason, Hariharan, Pushpa, Hindenach, Barbara, Hoadley, Katherine A., Huang, Jasmine, Ittmann, Michael M., Johnson, Ashlie, Jones, Corbin D., Ketchum, Karen A., Kirby, Justin, Le, Toan, Ma'ayan, Avi, Madan, Rashna, Mareedu, Sailaja, McGarvey, Peter B., Modugno, Francesmary, Montgomery, Rebecca, Nyce, Kristen, Paulovich, Amanda G., Pruetz, Barbara L., Qi, Liqun, Richey, Shannon, Schadt, Eric E., Shutack, Yvonne, Singh, Shilpi, Smith, Michael, Tansil, Darlene, Thangudu, Ratna R., Tobin, Matt, Um, Ki Sung, Vatanian, Negin, Webster, Alex, Wilson, George D., Wright, Jason, Zaalishvili, Kakhaber, Zhang, Zhen, Zhao, Grace, Dou, Yongchao, Katsnelson, Lizabeth, Gritsenko, Marina A., Hu, Yingwei, Reva, Boris, Hong, Runyu, Wang, Yi-Ting, Kolodziejczak, Iga, Lu, Rita Jui-Hsien, Tsai, Chia-Feng, Bu, Wen, Liu, Wenke, Guo, Xiaofang, An, Eunkyung, Arend, Rebecca C., Bavarva, Jasmin, Chen, Lijun, Chu, Rosalie K., Czekański, Andrzej, Davoli, Teresa, Demicco, Elizabeth G., DeLair, Deborah, Devereaux, Kelly, Dhanasekaran, Saravana M., Dottino, Peter, Dover, Bailee, Fillmore, Thomas L., Foxall, McKenzie, Hermann, Catherine E., Hiltke, Tara, Hostetter, Galen, Jędryka, Marcin, Jewell, Scott D., Johnson, Isabelle, Kahn, Andrea G., Ku, Amy T., Kumar-Sinha, Chandan, Kurzawa, Paweł, Lazar, Alexander J., Lazcano, Rossana, Lei, Jonathan T., Li, Yi, Liao, Yuxing, Lih, Tung-Shing M., Lin, Tai-Tu, Martignetti, John A., Masand, Ramya P., Matkowski, Rafał, McKerrow, Wilson, Mesri, Mehdi, Monroe, Matthew E., Moon, Jamie, Moore, Ronald J., Nestor, Michael D., Newton, Chelsea, Omelchenko, Tatiana, Omenn, Gilbert S., Payne, Samuel H., Petyuk, Vladislav A., Robles, Ana I., Rodriguez, Henry, Ruggles, Kelly V., Rykunov, Dmitry, Savage, Sara R., Schepmoes, Athena A., Shi, Tujin, Shi, Zhiao, Tan, Jimin, Taylor, Mason, Thiagarajan, Mathangi, Wang, Joshua M., Weitz, Karl K., Wen, Bo, Williams, C.M., Wu, Yige, Wyczalkowski, Matthew A., Yi, Xinpei, Zhang, Xu, Zhao, Rui, Mutch, David, Chinnaiyan, Arul M., Smith, Richard D., Nesvizhskii, Alexey I., Wang, Pei, Wiznerowicz, Maciej, Ding, Li, Mani, D.R., Zhang, Hui, Anderson, Matthew L., Rodland, Karin D., Zhang, Bing, Liu, Tao, and Fenyö, David

Published
2023
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25. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Author

Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A, Dennis, Joe, Tyrer, Jonathan P, Barnes, Daniel R, McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K, Adank, Muriel A, Agata, Simona, Ahearn, Thomas, Aittomäki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J, Arun, Banu K, Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heiko, Bermisheva, Marina, Bernstein, Leslie, Białkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E, Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S, Caldés, Trinidad, Caligo, Maria A, Campa, Daniele, Carter, Brian D, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Chung, Wendy K, Claes, Kathleen BM, Clarke, Christine L, GEMO Study Collaborators, EMBRACE Collaborators, Collée, J Margriet, Conroy, Don M, Czene, Kamila, Daly, Mary B, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M, Dörk, Thilo, Dos-Santos-Silva, Isabel, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Eliassen, A Heather, Engel, Christoph, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M, Garber, Judy, Garcia-Barberan, Vanesa, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, Gayther, Simon A, Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Greene, Mark H, Guénel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A, Hart, Steven N, He, Wei, Hogervorst, Frans BL, Hollestelle, Antoinette, and Hopper, John L

Subjects
GEMO Study Collaborators, EMBRACE Collaborators, KConFab Investigators, HEBON Investigators, ABCTB Investigators, Humans, Breast Neoplasms, Genetic Predisposition to Disease, BRCA1 Protein, BRCA2 Protein, Risk Factors, Genotype, Linkage Disequilibrium, Mutation, Polymorphism, Single Nucleotide, Alleles, Quantitative Trait Loci, Adult, Middle Aged, Female, Genome-Wide Association Study, Breast Cancer, Prevention, Cancer, Genetic Testing, Human Genome, Genetics, 2.1 Biological and endogenous factors
Abstract

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P

Published
2021

26. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Author

Barnes, Daniel R, Rookus, Matti A, McGuffog, Lesley, Leslie, Goska, Mooij, Thea M, Dennis, Joe, Mavaddat, Nasim, Adlard, Julian, Ahmed, Munaza, Aittomäki, Kristiina, Andrieu, Nadine, Andrulis, Irene L, Arnold, Norbert, Arun, Banu K, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barrowdale, Daniel, Benitez, Javier, Berthet, Pascaline, Białkowska, Katarzyna, Blanco, Amie M, Blok, Marinus J, Bonanni, Bernardo, Boonen, Susanne E, Borg, Åke, Bozsik, Aniko, Bradbury, Angela R, Brennan, Paul, Brewer, Carole, Brunet, Joan, Buys, Saundra S, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Christensen, Lise Lotte, Chung, Wendy K, Claes, Kathleen BM, Colas, Chrystelle, Collonge-Rame, Marie-Agnès, Cook, Jackie, Daly, Mary B, Davidson, Rosemarie, de la Hoya, Miguel, de Putter, Robin, Delnatte, Capucine, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M, Dorfling, Cecilia M, Dumont, Martine, Eeles, Ros, Ejlertsen, Bent, Engel, Christoph, Evans, D Gareth, Faivre, Laurence, Foretova, Lenka, Fostira, Florentia, Friedlander, Michael, Friedman, Eitan, Frost, Debra, Ganz, Patricia A, Garber, Judy, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K, Goldgar, David E, González-Neira, Anna, Greene, Mark H, Gschwantler-Kaulich, Daphne, Hahnen, Eric, Hamann, Ute, Hanson, Helen, Hentschel, Julia, Hogervorst, Frans BL, Hooning, Maartje J, Horvath, Judit, Hu, Chunling, Hulick, Peter J, Imyanitov, Evgeny N, Isaacs, Claudine, Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, James, Paul A, Janavicius, Ramunas, John, Esther M, Joseph, Vijai, Karlan, Beth Y, Kast, Karin, Koudijs, Marco, Kruse, Torben A, Kwong, Ava, Laitman, Yael, Lasset, Christine, and Lazaro, Conxi

Subjects
Clinical Research, Cancer, Ovarian Cancer, Prevention, Rare Diseases, Breast Cancer, 2.1 Biological and endogenous factors, Aetiology, BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, Carcinoma, Ovarian Epithelial, Female, Genetic Predisposition to Disease, Heterozygote, Humans, Mutation, Ovarian Neoplasms, Prospective Studies, Retrospective Studies, Risk Factors, BRCA1, 2, breast cancer, ovarian cancer, PRS, genetics, GEMO Study Collaborators, EMBRACE Collaborators, kConFab Investigators, HEBON Investigators, GENEPSO Investigators, Consortium of Investigators of Modifiers of BRCA and BRCA2, BRCA1/2, Genetics, Clinical Sciences, Genetics & Heredity
Abstract

PurposeWe assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers.MethodsRetrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort.ResultsThe ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10-72). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10-50). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10-22) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10-12) carriers. The associations in the prospective cohort were similar.ConclusionPopulation-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.

Published
2020

27. Transcriptome‐wide association study of breast cancer risk by estrogen‐receptor status

Author

Feng, Helian, Gusev, Alexander, Pasaniuc, Bogdan, Wu, Lang, Long, Jirong, Abu‐full, Zomoroda, Aittomäki, Kristiina, Andrulis, Irene L, Anton‐Culver, Hoda, Antoniou, Antonis C, Arason, Adalgeir, Arndt, Volker, Aronson, Kristan J, Arun, Banu K, Asseryanis, Ella, Auer, Paul L, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barnes, Daniel R, Barrowdale, Daniel, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Białkowska, Katarzyna, Blanco, Ana, Blomqvist, Carl, Boeckx, Bram, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Broeks, Annegien, Brüning, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Canisius, Sander, Campa, Daniele, Carter, Brian D, Carter, Jonathan, Castelao, Jose E, Chang‐Claude, Jenny, Chanock, Stephen J, Christiansen, Hans, Chung, Wendy K, Claes, Kathleen BM, Clarke, Christine L, Collaborators, GEMO Study, Collaborators, EMBRACE, Collaborators, GC‐HBOC study, Couch, Fergus J, Cox, Angela, Cross, Simon S, Cybulski, Cezary, Czene, Kamila, Daly, Mary B, de la Hoya, Miguel, De Leeneer, Kim, Dennis, Joe, Devilee, Peter, Diez, Orland, Domchek, Susan M, Dörk, Thilo, dos‐Santos‐Silva, Isabel, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Ejlertsen, Bent, Ellberg, Carolina, Engel, Christoph, Eriksson, Mikael, Fasching, Peter A, Fletcher, Olivia, Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gabrielson, Marike, Ganz, Patricia A, Gapstur, Susan M, Garber, Judy, García‐Closas, Montserrat, García‐Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Glendon, Gord, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González‐Neira, Anna, and Greene, Mark H

Subjects
Biological Sciences, Health Sciences, Genetics, Cancer, Biotechnology, Prevention, Clinical Research, Human Genome, Estrogen, Breast Cancer, Aetiology, 2.1 Biological and endogenous factors, Breast Neoplasms, Estrogens, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Humans, Receptors, Estrogen, Risk Assessment, Transcriptome, Vesicular Transport Proteins, breast cancer subtype, causal gene, GWAS, TWAS, GEMO Study Collaborators, EMBRACE Collaborators, GC-HBOC study Collaborators, ABCTB Investigators, HEBON Investigators, BCFR Investigators, OCGN Investigators, Public Health and Health Services, Epidemiology
Abstract

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.

Published
2020

28. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Author

Zhang, Haoyu, Ahearn, Thomas U, Lecarpentier, Julie, Barnes, Daniel, Beesley, Jonathan, Qi, Guanghao, Jiang, Xia, O'Mara, Tracy A, Zhao, Ni, Bolla, Manjeet K, Dunning, Alison M, Dennis, Joe, Wang, Qin, Ful, Zumuruda Abu, Aittomäki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Arun, Banu K, Auer, Paul L, Azzollini, Jacopo, Barrowdale, Daniel, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bialkowska, Katarzyna, Blanco, Ana, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Bondavalli, Davide, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Broeks, Annegien, Brucker, Sara Y, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Byers, Helen, Caldés, Trinidad, Caligo, Maria A, Calvello, Mariarosaria, Campa, Daniele, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Christiaens, Melissa, Christiansen, Hans, Chung, Wendy K, Claes, Kathleen BM, Clarke, Christine L, Cornelissen, Sten, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Diez, Orland, Domchek, Susan M, Dörk, Thilo, Dwek, Miriam, Eccles, Diana M, Ekici, Arif B, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Foretova, Lenka, Fostira, Florentia, Friedman, Eitan, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M, Garber, Judy, García-Sáenz, José A, Gaudet, Mia M, Gayther, Simon A, Giles, Graham G, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Greene, Mark H, Gronwald, Jacek, Guénel, Pascal, Häberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Hake, Christopher R, Hall, Per, Hamann, Ute, Harkness, Elaine F, Heemskerk-Gerritsen, Bernadette AM, and Hillemanns, Peter

Subjects
kConFab Investigators, ABCTB Investigators, EMBRACE Study, GEMO Study Collaborators, Humans, Breast Neoplasms, Genetic Predisposition to Disease, BRCA1 Protein, Case-Control Studies, Linkage Disequilibrium, Mutation, Female, Genome-Wide Association Study, Triple Negative Breast Neoplasms, Human Genome, Cancer, Prevention, Genetics, Breast Cancer, 2.1 Biological and endogenous factors, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P

Published
2020

31. Cisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): a randomised, double-blind, placebo-controlled, phase 2 trial

Author

Rodler, Eve, Sharma, Priyanka, Barlow, William E, Gralow, Julie R, Puhalla, Shannon L, Anders, Carey K, Goldstein, Lori, Tripathy, Debu, Brown-Glaberman, Ursa A, Huynh, Thu-Tam, Szyarto, Christopher S, Godwin, Andrew K, Pathak, Harsh B, Swisher, Elizabeth M, Radke, Marc R, Timms, Kirsten M, Lew, Danika L, Miao, Jieling, Pusztai, Lajos, Hayes, Daniel F, and Hortobagyi, Gabriel N

Published
2023
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33. Ductal carcinoma in situ: Molecular and cellular basis of malignancy.

Author

Behbod, Fariba, primary, Arslan, Emre, additional, Zhu, Qian, additional, Hong, Yan, additional, Strope, Benjamin, additional, Wagner, Jamie L., additional, Larson, Kelsey E., additional, Fields, Timothy, additional, Aripoli, Allison, additional, Huppe, Ashley, additional, Winblad, Onalisa, additional, Balanoff, Christa, additional, Peterson, Jessica, additional, Hill, Molly, additional, Smith, Camron, additional, Chang, Eric, additional, Godwin, Andrew K., additional, Khan, Seema Ahsan, additional, Fabian, Carol J., additional, and Rai, Kunal, additional

Published
2024
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34. NeoTRACT: Phase II trial of neoadjuvant tumor infiltrating lymphocyte- and response-adapted chemoimmunotherapy for triple-negative breast cancer (TNBC).

Author

Stecklein, Shane R., primary, Aripoli, Allison, additional, Salgado, Roberto, additional, O'Dea, Anne, additional, Nye, Lauren Elizabeth, additional, Larson, Kelsey E., additional, Satelli, Deepti, additional, Rader, Ryan, additional, Madan, Rashna, additional, Yoder, Rachel, additional, Staley, Joshua M., additional, Fernandez, India, additional, Heinrich, Adam, additional, Wagner, Jamie L., additional, Balanoff, Christa, additional, Kilgore, Lyndsey, additional, Bantis, Leonidas, additional, Godwin, Andrew K., additional, Khan, Qamar J., additional, and Sharma, Priyanka, additional

Published
2024
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35. Correlation of serum anti-Müllerian hormone (AMH) levels on identification of premenopausal patients (pts) with hormone receptor positive (HR+), HER2-negative, node-positive breast cancer most likely to benefit from adjuvant chemotherapy in SWOG S1007 (RxPONDER).

Author

Kalinsky, Kevin, primary, Barlow, William E., additional, Pathak, Harsh B, additional, Gralow, Julie R., additional, Albain, Kathy S., additional, Hayes, Daniel F., additional, Lin, Nancy U., additional, Perez, Edith A., additional, Goldstein, Lori J., additional, Chia, Stephen K. L., additional, Rastogi, Priya, additional, Schott, Anne F., additional, Shak, Steven, additional, Tripathy, Debashish, additional, Hortobagyi, Gabriel N., additional, Meric-Bernstam, Funda, additional, Sharma, Priyanka, additional, Pusztai, Lajos, additional, Thompson, Alastair Mark, additional, and Godwin, Andrew K., additional

Published
2024
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36. Prospective longitudinal study of kinetics of humoral response to one, two, or three doses of SARS-CoV-2 vaccine in hematopoietic cell transplant recipients

Author

Khan, Qamar J., Bivona, Cory R., Liu, Ben, Nelson, Maggie, Martin, Grace A., Mushtaq, Muhammad Umair, Sharma, Priyanka, Streeter, Natalie R., Hoffmann, Marc, Doolittle, Gary C., Zhong, Cuncong, Mitchell, Laura, Li, Kevin H., Pessetto, Ziyan Y., Ghosh, Arnab, Pathak, Harsh B., Zhang, Jun, Godwin, Andrew K., and McGuirk, Joseph P.

Published
2022
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38. Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Author

Qian, Frank, Rookus, Matti A, Leslie, Goska, Risch, Harvey A, Greene, Mark H, Aalfs, Cora M, Adank, Muriel A, Adlard, Julian, Agnarsson, Bjarni A, Ahmed, Munaza, Aittomäki, Kristiina, Andrulis, Irene L, Arnold, Norbert, Arun, Banu K, Ausems, Margreet GEM, Azzollini, Jacopo, Barrowdale, Daniel, Barwell, Julian, Benitez, Javier, Białkowska, Katarzyna, Bonadona, Valérie, Borde, Julika, Borg, Ake, Bradbury, Angela R, Brunet, Joan, Buys, Saundra S, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Carter, Jonathan, Chiquette, Jocelyne, Chung, Wendy K, Claes, Kathleen BM, Collée, J Margriet, Collonge-Rame, Marie-Agnès, Couch, Fergus J, Daly, Mary B, Delnatte, Capucine, Diez, Orland, Domchek, Susan M, Dorfling, Cecilia M, Eason, Jacqueline, Easton, Douglas F, Eeles, Ros, Engel, Christoph, Evans, D Gareth, Faivre, Laurence, Feliubadaló, Lidia, Foretova, Lenka, Friedman, Eitan, Frost, Debra, Ganz, Patricia A, Garber, Judy, Garcia-Barberan, Vanesa, Gehrig, Andrea, Glendon, Gord, Godwin, Andrew K, Gómez Garcia, Encarna B, Hamann, Ute, Hauke, Jan, Hopper, John L, Hulick, Peter J, Imyanitov, Evgeny N, Isaacs, Claudine, Izatt, Louise, Jakubowska, Anna, Janavicius, Ramunas, John, Esther M, Karlan, Beth Y, Kets, Carolien M, Laitman, Yael, Lázaro, Conxi, Leroux, Dominique, Lester, Jenny, Lesueur, Fabienne, Loud, Jennifer T, Lubiński, Jan, Łukomska, Alicja, McGuffog, Lesley, Mebirouk, Noura, Meijers-Heijboer, Hanne EJ, Meindl, Alfons, Miller, Austin, Montagna, Marco, Mooij, Thea M, Mouret-Fourme, Emmanuelle, Nathanson, Katherine L, Nehoray, Bita, Neuhausen, Susan L, Nevanlinna, Heli, Nielsen, Finn C, Offit, Kenneth, Olah, Edith, Ong, Kai-ren, Oosterwijk, Jan C, Ottini, Laura, Parsons, Michael T, Peterlongo, Paolo, Pfeiler, Georg, and Pradhan, Nisha

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Prevention, Ovarian Cancer, Breast Cancer, Genetics, Aging, Cancer, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Body Height, Body Mass Index, Female, Genes, BRCA1, Genes, BRCA2, Heterozygote, Humans, Mendelian Randomization Analysis, Menopause, Middle Aged, Mutation, Ovarian Neoplasms, Proportional Hazards Models, KConFab Investigators, HEBON Investigators, GEMO Study Collaborators, EMBRACE Collaborators, CIMBA, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundHeight and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown.MethodsWe applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models.ResultsObserved height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction

Published
2019

39. Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.

Author

Ferreira, Manuel A, Gamazon, Eric R, Al-Ejeh, Fares, Aittomäki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Arason, Adalgeir, Arndt, Volker, Aronson, Kristan J, Arun, Banu K, Asseryanis, Ella, Azzollini, Jacopo, Balmaña, Judith, Barnes, Daniel R, Barrowdale, Daniel, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Białkowska, Katarzyna, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Broeks, Annegien, Burwinkel, Barbara, Caldés, Trinidad, Caligo, Maria A, Campa, Daniele, Campbell, Ian, Canzian, Federico, Carter, Jonathan, Carter, Brian D, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Christiansen, Hans, Chung, Wendy K, Claes, Kathleen BM, Clarke, Christine L, EMBRACE Collaborators, GC-HBOC Study Collaborators, GEMO Study Collaborators, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, de la Hoya, Miguel, Dennis, Joe, Devilee, Peter, Diez, Orland, Dörk, Thilo, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Ejlertsen, Bent, Ellberg, Carolina, Engel, Christoph, Eriksson, Mikael, Fasching, Peter A, Fletcher, Olivia, Flyger, Henrik, Friedman, Eitan, Frost, Debra, Gabrielson, Marike, Gago-Dominguez, Manuela, Ganz, Patricia A, Gapstur, Susan M, Garber, Judy, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Glendon, Gord, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Greene, Mark H, Gronwald, Jacek, Guénel, Pascal, Haiman, Christopher A, Hall, Per, Hamann, Ute, He, Wei, Heyworth, Jane, Hogervorst, Frans BL, Hollestelle, Antoinette, Hoover, Robert N, Hopper, John L, Hulick, Peter J, Humphreys, Keith, Imyanitov, Evgeny N, ABCTB Investigators, HEBON Investigators, and BCFR Investigators

Subjects
EMBRACE Collaborators, GC-HBOC Study Collaborators, GEMO Study Collaborators, ABCTB Investigators, HEBON Investigators, BCFR Investigators, Humans, Breast Neoplasms, Genetic Predisposition to Disease, Gene Expression Profiling, Quantitative Trait Loci, Female, Genome-Wide Association Study, Prevention, Cancer, Human Genome, Aging, Breast Cancer, Genetics, Biotechnology, 2.1 Biological and endogenous factors
Abstract

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.

Published
2019

40. Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study.

Author

Qian, Frank, Wang, Shengfeng, Mitchell, Jonathan, McGuffog, Lesley, Barrowdale, Daniel, Leslie, Goska, Oosterwijk, Jan C, Chung, Wendy K, Evans, D Gareth, Engel, Christoph, Kast, Karin, Aalfs, Cora M, Adank, Muriel A, Adlard, Julian, Agnarsson, Bjarni A, Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L, Arun, Banu K, Ausems, Margreet GEM, Azzollini, Jacopo, Barouk-Simonet, Emmanuelle, Barwell, Julian, Belotti, Muriel, Benitez, Javier, Berger, Andreas, Borg, Ake, Bradbury, Angela R, Brunet, Joan, Buys, Saundra S, Caldes, Trinidad, Caligo, Maria A, Campbell, Ian, Caputo, Sandrine M, Chiquette, Jocelyne, Claes, Kathleen BM, Margriet Collée, J, Couch, Fergus J, Coupier, Isabelle, Daly, Mary B, Davidson, Rosemarie, Diez, Orland, Domchek, Susan M, Donaldson, Alan, Dorfling, Cecilia M, Eeles, Ros, Feliubadaló, Lidia, Foretova, Lenka, Fowler, Jeffrey, Friedman, Eitan, Frost, Debra, Ganz, Patricia A, Garber, Judy, Garcia-Barberan, Vanesa, Glendon, Gord, Godwin, Andrew K, Gómez Garcia, Encarna B, Gronwald, Jacek, Hahnen, Eric, Hamann, Ute, Henderson, Alex, Hendricks, Carolyn B, Hopper, John L, Hulick, Peter J, Imyanitov, Evgeny N, Isaacs, Claudine, Izatt, Louise, Izquierdo, Ángel, Jakubowska, Anna, Kaczmarek, Katarzyna, Kang, Eunyoung, Karlan, Beth Y, Kets, Carolien M, Kim, Sung-Won, Kim, Zisun, Kwong, Ava, Laitman, Yael, Lasset, Christine, Hyuk Lee, Min, Won Lee, Jong, Lee, Jihyoun, Lester, Jenny, Lesueur, Fabienne, Loud, Jennifer T, Lubinski, Jan, Mebirouk, Noura, Meijers-Heijboer, Hanne EJ, Meindl, Alfons, Miller, Austin, Montagna, Marco, Mooij, Thea M, Morrison, Patrick J, Mouret-Fourme, Emmanuelle, Nathanson, Katherine L, Neuhausen, Susan L, Nevanlinna, Heli, Niederacher, Dieter, Nielsen, Finn C, Nussbaum, Robert L, and Offit, Kenneth

Subjects
GEMO Study Collaborators, HEBON, EMBRACE, Humans, Breast Neoplasms, Genetic Predisposition to Disease, BRCA1 Protein, BRCA2 Protein, Body Mass Index, Body Height, Prognosis, Risk Factors, Mutation, Polymorphism, Single Nucleotide, Adult, Female, Mendelian Randomization Analysis, Oncology & Carcinogenesis, Oncology and Carcinogenesis
Abstract

BackgroundBRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear.MethodsWe used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants. We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided.ResultsObserved height was positively associated with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P = 1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P = .47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m2 increase, HR = 0.94, 95% CI = 0.90 to 0.98; P = .007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P = .02). BMI was primarily associated with premenopausal breast cancer.ConclusionHeight is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management.

Published
2019

42. Impact of low versus negative estrogen/progesterone receptor status on clinico-pathologic characteristics and survival outcomes in HER2-negative breast cancer

Author

Yoder, Rachel, Kimler, Bruce F., Staley, Joshua M., Schwensen, Kelsey, Wang, Yen Y., Finke, Karissa, O’Dea, Anne, Nye, Lauren, Elia, Manana, Crane, Gregory, McKittrick, Richard, Pluenneke, Robert, Madhusudhana, Sheshadri, Beck, Larry, Shrestha, Anuj, Corum, Larry, Marsico, Mark, Stecklein, Shane R., Godwin, Andrew K., Khan, Qamar J., and Sharma, Priyanka

Published
2022
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44. Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients

Author

Adamson, Kathi, Albain, Kathy S., Asare, Adam L., Asare, Smita M., Balassanian, Ron, Beckwith, Heather, Berry, Scott M., Berry, Donald A., Boughey, Judy C., Buxton, Meredith B., Chen, Yunn-Yi, Chen, Beiyun, Chien, A. Jo, Chui, Stephen Y., Clark, Amy S., Clennell, Julia L., Datnow, Brian, DeMichele, Angela M., Duan, Xiuzhen, Edmiston, Kirsten K., Elias, Anthony D., Ellis, Erin D., Esserman, Laura L., Euhus, David M., Fadare, Oluwole, Fan, Fang, Feldman, Michael D, Forero-Torres, Andres, Haley, Barbara B., Han, Hyo S., Harada, Shuko, Haugen, Patricia, Helsten, Teresa, Hirst, Gillian L., Hylton, Nola M., Isaacs, Claudine, Kemmer, Kathleen, Khan, Qamar J., Khazai, Laila, Klein, Molly E., Krings, Gregor, Lang, Julie E., LeBeau, Lauren G., Leyland-Jones, Brian, Liu, Minetta C., Lo, Shelly, Lu, Janice, Magliocco, Anthony, Matthews, Jeffrey B., Melisko, Michelle E., Mhawech-Fauceglia, Paulette, Moulder, Stacy L., Murthy, Rashmi K., Nanda, Rita, Northfelt, Donald W., Ocal, Idris T., Olopade, Olufunmilayo, Pambuccian, Stefan, Paoloni, Melissa, Park, John W., Parker, Barbara A., Perlmutter, Jane, Peterson, Garry, Pusztai, Lajos, Rendi, Mara, Rugo, Hope S., Sahoo, Sunati, Sams, Sharon, Sanil, Ashish, Sattar, Husain, Schwab, Richard B., Singhrao, Ruby, Steeg, Katherine, Stringer-Reasor, Erica, Symmans, W. Fraser, Tawfik, Ossama, Tripathy, Debasish, Troxell, Megan L., van't Veer, Laura J., Venters, Sara J., Vinh, Tuyethoa, Viscusi, Rebecca K., Wallace, Anne M., Wei, Shi, Wilson, Amy, Yau, Christina, Yee, Douglas, Zeck, Jay C., Osdoit, Marie, van der Noordaa, Marieke, Shad, Sonal, Wei, Jane, de Croze, Diane, Hamy, Anne-Sophie, Laé, Marick, Reyal, Fabien, Sonke, Gabe S, Steenbruggen, Tessa G, van Seijen, Maartje, Wesseling, Jelle, Martín, Miguel, del Monte-Millán, Maria, López-Tarruella, Sara, Boughey, Judy C, Goetz, Matthew P, Hoskin, Tanya, Gould, Rebekah, Valero, Vicente, Edge, Stephen B, Abraham, Jean E, Bartlett, John M S, Caldas, Carlos, Dunn, Janet, Earl, Helena, Hayward, Larry, Hiller, Louise, Provenzano, Elena, Sammut, Stephen-John, Thomas, Jeremy S, Cameron, David, Graham, Ashley, Hall, Peter, Mackintosh, Lorna, Godwin, Andrew K, Schwensen, Kelsey, Sharma, Priyanka, DeMichele, Angela M, Cole, Kimberly, Kim, Mi-Ok, van 't Veer, Laura J, Esserman, Laura J, and Symmans, W Fraser

Published
2022
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45. Targeting progesterone signaling prevents metastatic ovarian cancer

Author

Kim, Olga, Park, Eun Young, Kwon, Sun Young, Shin, Sojin, Emerson, Robert E., Shin, Yong-Hyun, DeMayo, Francesco J., Lydon, John P., Coffey, Donna M., Hawkins, Shannon M., Quilliam, Lawrence A., Cheon, Dong-Joo, Fernández, Facundo M., Nephew, Kenneth P., Karpf, Adam R., Widschwendter, Martin, Sood, Anil K., Bast, Robert C., Godwin, Andrew K., Miller, Kathy D., Cho, Chi-Heum, and Kim, Jaeyeon

Published
2020

46. A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk

Author

Lu, Yingchang, Beeghly-Fadiel, Alicia, Wu, Lang, Guo, Xingyi, Li, Bingshan, Schildkraut, Joellen M, Im, Hae Kyung, Chen, Yian A, Permuth, Jennifer B, Reid, Brett M, Teer, Jamie K, Moysich, Kirsten B, Andrulis, Irene L, Anton-Culver, Hoda, Arun, Banu K, Bandera, Elisa V, Barkardottir, Rosa B, Barnes, Daniel R, Benitez, Javier, Bjorge, Line, Brenton, James, Butzow, Ralf, Caldes, Trinidad, Caligo, Maria A, Campbell, Ian, Chang-Claude, Jenny, Claes, Kathleen BM, Couch, Fergus J, Cramer, Daniel W, Daly, Mary B, deFazio, Anna, Dennis, Joe, Diez, Orland, Domchek, Susan M, Dörk, Thilo, Easton, Douglas F, Eccles, Diana M, Fasching, Peter A, Fortner, Renée T, Fountzilas, George, Friedman, Eitan, Ganz, Patricia A, Garber, Judy, Giles, Graham G, Godwin, Andrew K, Goldgar, David E, Goodman, Marc T, Greene, Mark H, Gronwald, Jacek, Hamann, Ute, Heitz, Florian, Hildebrandt, Michelle AT, Høgdall, Claus K, Hollestelle, Antoinette, Hulick, Peter J, Huntsman, David G, Imyanitov, Evgeny N, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Karlan, Beth Y, Kelemen, Linda E, Kiemeney, Lambertus A, Kjaer, Susanne K, Kwong, Ava, Le, Nhu D, Leslie, Goska, Lesueur, Fabienne, Levine, Douglas A, Mattiello, Amalia, May, Taymaa, McGuffog, Lesley, McNeish, Iain A, Merritt, Melissa A, Modugno, Francesmary, Montagna, Marco, Neuhausen, Susan L, Nevanlinna, Heli, Nielsen, Finn C, Nikitina-Zake, Liene, Nussbaum, Robert L, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I, Olson, Sara H, Olsson, Håkan, Osorio, Ana, Park, Sue K, Parsons, Michael T, Peeters, Petra HM, Pejovic, Tanja, Peterlongo, Paolo, Phelan, Catherine M, Pujana, Miquel Angel, Ramus, Susan J, Rennert, Gad, Risch, Harvey, Rodriguez, Gustavo C, Rodríguez-Antona, Cristina, and Romieu, Isabelle

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Prevention, Human Genome, Ovarian Cancer, Rare Diseases, Cancer, 2.1 Biological and endogenous factors, Aetiology, Carcinogenesis, Carcinoma, Ovarian Epithelial, Cohort Studies, Female, Gene Expression Profiling, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Prognosis, Quantitative Trait Loci, Risk Factors, Transcriptome, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10-6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10-7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10-3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419-30. ©2018 AACR.

Published
2018

47. The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Author

Ricketts, Christopher J, De Cubas, Aguirre A, Fan, Huihui, Smith, Christof C, Lang, Martin, Reznik, Ed, Bowlby, Reanne, Gibb, Ewan A, Akbani, Rehan, Beroukhim, Rameen, Bottaro, Donald P, Choueiri, Toni K, Gibbs, Richard A, Godwin, Andrew K, Haake, Scott, Hakimi, A Ari, Henske, Elizabeth P, Hsieh, James J, Ho, Thai H, Kanchi, Rupa S, Krishnan, Bhavani, Kwiatkowski, David J, Lui, Wembin, Merino, Maria J, Mills, Gordon B, Myers, Jerome, Nickerson, Michael L, Reuter, Victor E, Schmidt, Laura S, Shelley, C Simon, Shen, Hui, Shuch, Brian, Signoretti, Sabina, Srinivasan, Ramaprasad, Tamboli, Pheroze, Thomas, George, Vincent, Benjamin G, Vocke, Cathy D, Wheeler, David A, Yang, Lixing, Kim, William Y, Robertson, A Gordon, Spellman, Paul, Rathmell, W Kimryn, Linehan, W Marston, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Liu, Yuexin, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Broom, Bradley M, Hegde, Apurva M, Ju, Zhenlin, Korkut, Anil, Li, Jun, Liang, Han, and Ling, Shiyun

Subjects
Biological Sciences, Cancer Genome Atlas Research Network, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

(Cell Reports 23, 313–326; April 3, 2018) In the originally published version of this article, the author list contained two errors. Specifically, David J. Kwiatkowski was misspelled as David J. Kwaitkowski, and William Y. Kim was inadvertently written as William T. Kim. Both names have been corrected online. The authors regret this error.

Published
2018

48. Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation

Author

Malta, Tathiane M, Sokolov, Artem, Gentles, Andrew J, Burzykowski, Tomasz, Poisson, Laila, Weinstein, John N, Kamińska, Bożena, Huelsken, Joerg, Omberg, Larsson, Gevaert, Olivier, Colaprico, Antonio, Czerwińska, Patrycja, Mazurek, Sylwia, Mishra, Lopa, Heyn, Holger, Krasnitz, Alex, Godwin, Andrew K, Lazar, Alexander J, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Liu, Yuexin, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, Broom, Bradley M, Hegde, Apurva M, Ju, Zhenlin, Kanchi, Rupa S, Korkut, Anil, Li, Jun, Liang, Han, Ling, Shiyun, Liu, Wenbin, Lu, Yiling, Mills, Gordon B, Ng, Kwok-Shing, Rao, Arvind, Ryan, Michael, Wang, Jing, Zhang, Jiexin, Abeshouse, Adam, Armenia, Joshua, Chakravarty, Debyani, Chatila, Walid K, de Bruijn, Ino, Gao, Jianjiong, Gross, Benjamin E, Heins, Zachary J, Kundra, Ritika, La, Konnor, Ladanyi, Marc, Luna, Augustin, Nissan, Moriah G, Ochoa, Angelica, Phillips, Sarah M, Reznik, Ed, and Sanchez-Vega, Francisco

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Stem Cell Research - Induced Pluripotent Stem Cell, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research, Human Genome, Cancer, Rare Diseases, Cancer Genomics, Genetics, Stem Cell Research - Nonembryonic - Human, Machine Learning and Artificial Intelligence, Good Health and Well Being, Carcinogenesis, Cell Dedifferentiation, DNA Methylation, Databases, Genetic, Epigenesis, Genetic, Humans, Machine Learning, MicroRNAs, Neoplasm Metastasis, Neoplasms, Stem Cells, Transcriptome, Tumor Microenvironment, Cancer Genome Atlas Research Network, The Cancer Genome Atlas, cancer stem cells, dedifferentiation, epigenomic, genomic, machine learning, pan-cancer, stemness, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation.

Published
2018

49. A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers

Author

Berger, Ashton C, Korkut, Anil, Kanchi, Rupa S, Hegde, Apurva M, Lenoir, Walter, Liu, Wenbin, Liu, Yuexin, Fan, Huihui, Shen, Hui, Ravikumar, Visweswaran, Rao, Arvind, Schultz, Andre, Li, Xubin, Sumazin, Pavel, Williams, Cecilia, Mestdagh, Pieter, Gunaratne, Preethi H, Yau, Christina, Bowlby, Reanne, Robertson, A Gordon, Tiezzi, Daniel G, Wang, Chen, Cherniack, Andrew D, Godwin, Andrew K, Kuderer, Nicole M, Rader, Janet S, Zuna, Rosemary E, Sood, Anil K, Lazar, Alexander J, Ojesina, Akinyemi I, Adebamowo, Clement, Adebamowo, Sally N, Baggerly, Keith A, Chen, Ting-Wen, Chiu, Hua-Sheng, Lefever, Steve, Liu, Liang, MacKenzie, Karen, Orsulic, Sandra, Roszik, Jason, Shelley, Carl Simon, Song, Qianqian, Vellano, Christopher P, Wentzensen, Nicolas, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, Broom, Bradley M, Ju, Zhenlin, Li, Jun, Liang, Han, and Ling, Shiyun

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Women's Health, Cancer, Cancer Genomics, Precision Medicine, Genetics, Human Genome, Breast Cancer, 4.1 Discovery and preclinical testing of markers and technologies, Breast Neoplasms, DNA Copy Number Variations, Databases, Genetic, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Genetic Predisposition to Disease, Genital Neoplasms, Female, Humans, Mutation, Organ Specificity, Prognosis, RNA, Long Noncoding, Receptors, Estrogen, Cancer Genome Atlas Research Network, TCGA, The Cancer Genome Atlas, breast cancer, cervical cancer, gynecologic cancer, omics, ovarian cancer, pan-gynecologic, uterine cancer, uterine carcinosarcoma, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories.

Published
2018

50. Selective targeting of IRAK1 attenuates low molecular weight hyaluronic acid-induced stemness and non-canonical STAT3 activation in epithelial ovarian cancer

Author

Standing, David, primary, Dandawate, Prasad, additional, Gunewardena, Sumedha, additional, Covarrubias-Zambrano, Obdulia, additional, Roby, Katherine F., additional, Khabele, Dineo, additional, Jewell, Andrea, additional, Tawfik, Ossama, additional, Bossmann, Stefan H., additional, Godwin, Andrew K., additional, Weir, Scott J., additional, Jensen, Roy A., additional, and Anant, Shrikant, additional

Published
2024
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