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1. Lessons learned from a candidate gene study investigating aromatase inhibitor treatment outcome in breast cancer

Author: Reiner Hoppe, Stefan Winter, Wing-Yee Lo, Kyriaki Michailidou, Manjeet K. Bolla, Renske Keeman, Qin Wang, Joe Dennis, Michael Lush, Krishna R. Kalari, Matthew P. Goetz, Liewei Wang, Junmei Cairns, Richard Weinshilboum, Lois Shepherd, Bingshu E. Chen, Lothar Häberle, Matthias Ruebner, Matthias W. Beckmann, Wei He, Nicole L. Larson, Sebastian M. Armasu, Werner Schroth, Balram Chowbay, Chiea Chuen Khor, Mustapha Abubakar, Antonis C. Antoniou, Thomas Brüning, Jose E. Castelao, Jenny Chang-Claude, NBCS Collaborators, Thilo Dörk, Diana M. Eccles, Jonine D. Figueroa, Manuela Gago-Dominguez, José A. García-Sáenz, Melanie Gündert, Carolin C. Hack, Ute Hamann, Sileny Han, Maartje J. Hooning, Hanna Huebner, ABCTB Investigators, Esther M. John, Yon-Dschun Ko, Vessela N. Kristensen, Sabine Linn, Sara Margolin, Dimitrios Mavroudis, Heli Nevanlinna, Patrick Neven, Nadia Obi, Tjoung-Won Park-Simon, Katri Pylkäs, Muhammad U. Rashid, Atocha Romero, Emmanouil Saloustros, Elinor J. Sawyer, William J. Tapper, Ian Tomlinson, Camilla Wendt, Robert Winqvist, Alison M. Dunning, Jacques Simard, Per Hall, Paul D. P. Pharoah, Matthias Schwab, Fergus J. Couch, Kamila Czene, Peter A. Fasching, Douglas F. Easton, Marjanka K. Schmidt, James N. Ingle, and Hiltrud Brauch
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract The role of germline genetics in adjuvant aromatase inhibitor (AI) treatment efficacy in ER-positive breast cancer is poorly understood. We employed a two-stage candidate gene approach to examine associations between survival endpoints and common germline variants in 753 endocrine resistance-related genes. For a discovery cohort, we screened the Breast Cancer Association Consortium database (n ≥ 90,000 cases) and retrieved 2789 AI-treated patients. Cox model-based analysis revealed 125 variants associated with overall, distant relapse-free, and relapse-free survival (p-value ≤ 1E-04). In validation analysis using five independent cohorts (n = 8857), none of the six selected candidates representing major linkage blocks at CELA2B/CASP9, NR1I2/GSK3B, LRP1B, and MIR143HG (CARMN) were validated. We discuss potential reasons for the failed validation and replication of published findings, including study/treatment heterogeneity and other limitations inherent to genomic treatment outcome studies. For the future, we envision prospective longitudinal studies with sufficiently long follow-up and endpoints that reflect the dynamic nature of endocrine resistance.
Published: 2025
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2. Assessment of MYC and TERT copy number variations in lung cancer using digital PCR

Author: Alexander Brik, Katharina Wichert, Daniel G. Weber, Katja Szafranski, Peter Rozynek, Swetlana Meier, Yon-Dschun Ko, Reinhard Büttner, Klaus Gerwert, Thomas Behrens, Thomas Brüning, and Georg Johnen
Subjects: Marker combination, Copy number variations, Digital polymerase chain reaction, Diagnosis, Non-small cell lung cancer, Frozen tissue, Medicine, Biology (General), QH301-705.5, Science (General), Q1-390
Abstract: Abstract Objective Lung cancer is the second most frequent cancer type and the most common cause of cancer-related deaths worldwide. Alteration of gene copy numbers are associated with lung cancer and the determination of copy number variations (CNV) is appropriate for the discrimination between tumor and non-tumor tissue in lung cancer. As telomerase reverse transcriptase (TERT) and v-myc avian myelocytomatosis viral oncogene homolog (MYC) play a role in lung cancer the aims of this study were the verification of our recent results analyzing MYC CNV in tumor and non-tumor tissue of lung cancer patients using an independent study group and the assessment of TERT CNV as an additional marker. Results TERT and MYC status was analyzed using digital PCR (dPCR) in tumor and adjacent non-tumor tissue samples of 114 lung cancer patients. The difference between tumor and non-tumor samples were statistically significant (p
Published: 2023
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3. A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry

Author: Pooja Middha, Xiaoliang Wang, Sabine Behrens, Manjeet K. Bolla, Qin Wang, Joe Dennis, Kyriaki Michailidou, Thomas U. Ahearn, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Kristan J. Aronson, Paul L. Auer, Annelie Augustinsson, Thaïs Baert, Laura E. Beane Freeman, Heiko Becher, Matthias W. Beckmann, Javier Benitez, Stig E. Bojesen, Hiltrud Brauch, Hermann Brenner, Angela Brooks-Wilson, Daniele Campa, Federico Canzian, Angel Carracedo, Jose E. Castelao, Stephen J. Chanock, Georgia Chenevix-Trench, CTS Consortium, Emilie Cordina-Duverger, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Laure Dossus, Pierre-Antoine Dugué, A. Heather Eliassen, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Jonine D. Figueroa, Olivia Fletcher, Henrik Flyger, Marike Gabrielson, Manuela Gago-Dominguez, Graham G. Giles, Anna González-Neira, Felix Grassmann, Anne Grundy, Pascal Guénel, Christopher A. Haiman, Niclas Håkansson, Per Hall, Ute Hamann, Susan E. Hankinson, Elaine F. Harkness, Bernd Holleczek, Reiner Hoppe, John L. Hopper, Richard S. Houlston, Anthony Howell, David J. Hunter, Christian Ingvar, ABCTB Investigators, kConFab Investigators, Karolin Isaksson, Helena Jernström, Esther M. John, Michael E. Jones, Rudolf Kaaks, Renske Keeman, Cari M. Kitahara, Yon-Dschun Ko, Stella Koutros, Allison W. Kurian, James V. Lacey, Diether Lambrechts, Nicole L. Larson, Susanna Larsson, Loic Le Marchand, Flavio Lejbkowicz, Shuai Li, Martha Linet, Jolanta Lissowska, Maria Elena Martinez, Tabea Maurer, Anna Marie Mulligan, Claire Mulot, Rachel A. Murphy, William G. Newman, Sune F. Nielsen, Børge G. Nordestgaard, Aaron Norman, Katie M. O’Brien, Janet E. Olson, Alpa V. Patel, Ross Prentice, Erika Rees-Punia, Gad Rennert, Valerie Rhenius, Kathryn J. Ruddy, Dale P. Sandler, Christopher G. Scott, Mitul Shah, Xiao-Ou Shu, Ann Smeets, Melissa C. Southey, Jennifer Stone, Rulla M. Tamimi, Jack A. Taylor, Lauren R. Teras, Katarzyna Tomczyk, Melissa A. Troester, Thérèse Truong, Celine M. Vachon, Sophia S. Wang, Clarice R. Weinberg, Hans Wildiers, Walter Willett, Stacey J. Winham, Alicja Wolk, Xiaohong R. Yang, M. Pilar Zamora, Wei Zheng, Argyrios Ziogas, Alison M. Dunning, Paul D. P. Pharoah, Montserrat García-Closas, Marjanka K. Schmidt, Peter Kraft, Roger L. Milne, Sara Lindström, Douglas F. Easton, and Jenny Chang-Claude
Subjects: Breast cancer, Gene-environment interactions, Genetic epidemiology, European ancestry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Genome-wide studies of gene–environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene–environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 × 10–5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability
Published: 2023
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4. Developing tumor-specific PRO-CTCAE item sets: analysis of a cross-sectional survey in three German outpatient cancer centers

Author: Maximilian Günther, Leopold Hentschel, Markus Schuler, Theresa Müller, Katharina Schütte, Yon-Dschun Ko, Ingo Schmidt-Wolf, and Ulrich Jaehde
Subjects: Patient-reported outcomes, PRO-CTCAE, Breast cancer, Symptom burden, Multiple myeloma, Prostate cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background To include the patient perspective in the assessment of adverse events in oncology, a patient-reported outcomes (PRO) version of the Common Terminology Criteria for Adverse Events (CTCAE) was developed by the US National Cancer Institute, the so called PRO-CTCAE. The objective of this study was the development of disease-specific PRO-CTCAE item sets for patients with breast cancer (BC), multiple myeloma (MM), and prostate cancer (PC). Methods The cross-sectional survey was conducted at three German outpatient cancer centers. Prevalence and importance of the 78 PRO-CTCAE symptoms were assessed using a patient questionnaire. To select the most relevant PRO-CTCAE items for each tumor entity, symptoms were ranked based on patient answers. Results 101 patients with BC, 107 with MM, and 66 with PC participated. The final item sets contained 21 symptoms (BC) or 19 symptoms (MM and PC), respectively. Eight symptoms (fatigue, muscle pain, insomnia, joint pain, general pain, dizziness, shortness of breath, and swelling) were represented in all three item sets. Fatigue was the symptom with the highest ranking across item sets followed by insomnia. Symptoms with the highest rankings represented in only one item set were symptoms affecting the urogenital system in the PC item set, blurred vision in the BC item set, and decreased appetite in the MM item set. Conclusions Individual PRO-CTCAE item sets for a German patient population were developed for the three tumor entities on the basis of patients’ differences in symptom profiles and perceptions. The quality and psychometric criteria of the newly compiled item sets should be evaluated in validation studies.
Published: 2023
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5. MR‐lymphangiography identifies lymphatic pathologies in patients with idiopathic recurrent cervical swelling

Author: Marius Vach, Julia Wagenpfeil, Andreas Henkel, Sebastian Strieth, Julian Alexander Luetkens, Yon‐Dschun Ko, Hans Heinz Schild, Ulrike Irmgard Attenberger, and Claus Christian Pieper
Subjects: cervical swelling, chylothorax, lymphangiography, lymphedema, magnetic resonance imaging, Otorhinolaryngology, RF1-547, Surgery, RD1-811
Abstract: Abstract Background Idiopathic recurrent cervical swelling may be caused by lymphatic abnormalities. Methods Ten patients (9 females, mean age 51.2 ± 7) with idiopathic recurrent cervical swelling underwent MR‐lymphangiography (MRL). MR‐lymphangiograms were evaluated regarding lymphatic anatomy and flow. Individualized treatment was recommended according to MRL‐findings. Results 8/10 patients presented with left‐sided, 2/10 with right‐sided swelling. Pathological lymph‐flow was identified in all cases: thoracic duct dilatation in patients with left‐sided and right lymphatic duct dilatation in right‐sided swelling, accessory thoracic lymphatics in 7/10 and reflux in 8/10 cases. In two cases, a lymphatic thrombus was identified. After treatment, symptoms resolved completely in 6/10 cases and partially in 1/10 cases. The remaining three patients have intermittent swellings but have no treatment wish. Conclusion Idiopathic recurrent cervical swelling can be caused by lymphatic anomalies. MRL displays impaired lymphatic drainage, lymphatic vessel dilatation, and chylolymphatic reflux as hallmarks of this condition and may aid in targeted treatment planning.
Published: 2022
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6. Medication risks in older patients (70 +) with cancer and their association with therapy-related toxicity

Author: Imke Ortland, Monique Mendel Ott, Michael Kowar, Christoph Sippel, Yon-Dschun Ko, Andreas H. Jacobs, and Ulrich Jaehde
Subjects: Polymedication, Potentially inappropriate medication, Drug-drug interactions, Older patients with cancer, Toxicity, Onco-geriatrics, Geriatrics, RC952-954.6
Abstract: Abstract Background To evaluate medication-related risks in older patients with cancer and their association with severe toxicity during antineoplastic therapy. Methods This is a secondary analysis of two prospective, single-center observational studies which included patients ≥ 70 years with cancer. The patients’ medication lists were investigated regarding possible risks: polymedication (defined as the use of ≥ 5 drugs), potentially inappropriate medication (PIM), and relevant potential drug-drug interactions (rPDDI). The risks were analyzed before and after start of cancer therapy. Severe toxicity during antineoplastic therapy was captured from medical records according to the Common Terminology Criteria for Adverse Events (CTCAE). The association between grade ≥ 3 toxicity and medication risks was evaluated by univariate as well as multivariate regression adjusted by ECOG and age. Results The study cohort comprised 136 patients (50% female, mean age 77 years, 42% hematological malignancies). Before the start of cancer therapy, patients took on average 5 drugs as long-term medication and 52% of patients were exposed to polymedication. More than half of patients used at least one PIM. Approximately one third of patients exhibited rPDDI. The prevalence of medication risks increased after start of cancer therapy. rPDDI were significantly associated with severe overall toxicity (OR, 5.07; p = 0.036; 95% Confidence Interval (CI) 1.11–23.14; toxicity in patients with rPDDI 94.1% (32/34) vs 75.9% (60/79) in patients without rPDDI) and hematological toxicity (OR, 3.95; p = 0.010; 95% CI 1.38–11.29; hematological toxicity in patients with rPDDI 85.3% (29/34) vs 59.5% (47/79) in patients without rPDDI). In the multivariate analysis adjusted by ECOG and age, only the association for rPDDI with hematological toxicity remained statistically significant (OR, 4.51; p = 0.007; 95% CI 1.52–13.38). These findings should be further investigated in larger studies. Conclusion Medication risks are common in older patients with cancer and might be associated with toxicity. This raises the need for tailored interventions to ensure medication safety in this patient cohort.
Published: 2022
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7. Breast cancer risks associated with missense variants in breast cancer susceptibility genes

Author: Leila Dorling, Sara Carvalho, Jamie Allen, Michael T. Parsons, Cristina Fortuno, Anna González-Neira, Stephan M. Heijl, Muriel A. Adank, Thomas U. Ahearn, Irene L. Andrulis, Päivi Auvinen, Heiko Becher, Matthias W. Beckmann, Sabine Behrens, Marina Bermisheva, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Michael Bremer, Ignacio Briceno, Nicola J. Camp, Archie Campbell, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Georgia Chenevix-Trench, NBCS Collaborators, J. Margriet Collée, Kamila Czene, Joe Dennis, Thilo Dörk, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Jonine Figueroa, Henrik Flyger, Marike Gabrielson, Manuela Gago-Dominguez, Montserrat García-Closas, Graham G. Giles, Gord Glendon, Pascal Guénel, Melanie Gündert, Andreas Hadjisavvas, Eric Hahnen, Per Hall, Ute Hamann, Elaine F. Harkness, Mikael Hartman, Frans B. L. Hogervorst, Antoinette Hollestelle, Reiner Hoppe, Anthony Howell, kConFab Investigators, SGBCC Investigators, Anna Jakubowska, Audrey Jung, Elza Khusnutdinova, Sung-Won Kim, Yon-Dschun Ko, Vessela N. Kristensen, Inge M. M. Lakeman, Jingmei Li, Annika Lindblom, Maria A. Loizidou, Artitaya Lophatananon, Jan Lubiński, Craig Luccarini, Michael J. Madsen, Arto Mannermaa, Mehdi Manoochehri, Sara Margolin, Dimitrios Mavroudis, Roger L. Milne, Nur Aishah Mohd Taib, Kenneth Muir, Heli Nevanlinna, William G. Newman, Jan C. Oosterwijk, Sue K. Park, Paolo Peterlongo, Paolo Radice, Emmanouil Saloustros, Elinor J. Sawyer, Rita K. Schmutzler, Mitul Shah, Xueling Sim, Melissa C. Southey, Harald Surowy, Maija Suvanto, Ian Tomlinson, Diana Torres, Thérèse Truong, Christi J. van Asperen, Regina Waltes, Qin Wang, Xiaohong R. Yang, Paul D. P. Pharoah, Marjanka K. Schmidt, Javier Benitez, Bas Vroling, Alison M. Dunning, Soo Hwang Teo, Anders Kvist, Miguel de la Hoya, Peter Devilee, Amanda B. Spurdle, Maaike P. G. Vreeswijk, and Douglas F. Easton
Subjects: Breast cancer, Genetic epidemiology, Risk prediction, Missense variants, Medicine, Genetics, QH426-470
Abstract: Abstract Background Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain. Methods We analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to five in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated. Results The most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1, and BRCA2, data were compatible with small subsets (approximately 7%, 2%, and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47–2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best fitting models were well calibrated in the validation set. Conclusions These results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility.
Published: 2022
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8. Rare germline copy number variants (CNVs) and breast cancer risk

Author: Joe Dennis, Jonathan P. Tyrer, Logan C. Walker, Kyriaki Michailidou, Leila Dorling, Manjeet K. Bolla, Qin Wang, Thomas U. Ahearn, Irene L. Andrulis, Hoda Anton-Culver, Natalia N. Antonenkova, Volker Arndt, Kristan J. Aronson, Laura E. Beane Freeman, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Natalia V. Bogdanova, Stig E. Bojesen, Hermann Brenner, Jose E. Castelao, Jenny Chang-Claude, Georgia Chenevix-Trench, Christine L. Clarke, NBCS Collaborators, J. Margriet Collée, CTS Consortium, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Peter Devilee, Thilo Dörk, Laure Dossus, A. Heather Eliassen, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Jonine Figueroa, Olivia Fletcher, Henrik Flyger, Lin Fritschi, Marike Gabrielson, Manuela Gago-Dominguez, Montserrat García-Closas, Graham G. Giles, Anna González-Neira, Pascal Guénel, Eric Hahnen, Christopher A. Haiman, Per Hall, Antoinette Hollestelle, Reiner Hoppe, John L. Hopper, Anthony Howell, ABCTB Investigators, kConFab/AOCS Investigators, Agnes Jager, Anna Jakubowska, Esther M. John, Nichola Johnson, Michael E. Jones, Audrey Jung, Rudolf Kaaks, Renske Keeman, Elza Khusnutdinova, Cari M. Kitahara, Yon-Dschun Ko, Veli-Matti Kosma, Stella Koutros, Peter Kraft, Vessela N. Kristensen, Katerina Kubelka-Sabit, Allison W. Kurian, James V. Lacey, Diether Lambrechts, Nicole L. Larson, Martha Linet, Alicja Ogrodniczak, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, Dimitrios Mavroudis, Roger L. Milne, Taru A. Muranen, Rachel A. Murphy, Heli Nevanlinna, Janet E. Olson, Håkan Olsson, Tjoung-Won Park-Simon, Charles M. Perou, Paolo Peterlongo, Dijana Plaseska-Karanfilska, Katri Pylkäs, Gad Rennert, Emmanouil Saloustros, Dale P. Sandler, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Rana Shibli, Ann Smeets, Penny Soucy, Melissa C. Southey, Anthony J. Swerdlow, Rulla M. Tamimi, Jack A. Taylor, Lauren R. Teras, Mary Beth Terry, Ian Tomlinson, Melissa A. Troester, Thérèse Truong, Celine M. Vachon, Camilla Wendt, Robert Winqvist, Alicja Wolk, Xiaohong R. Yang, Wei Zheng, Argyrios Ziogas, Jacques Simard, Alison M. Dunning, Paul D. P. Pharoah, and Douglas F. Easton
Subjects: Biology (General), QH301-705.5
Abstract: Dennis et al. investigate potential breast cancer associations with rare germline copy number variants (CNVs) by conducting a genome-wide analysis in a large breast cancer case-control dataset. The authors detected associations with exonic deletions in established breast cancer susceptibility genes and suggestive associations for a number of non-coding CNVs.
Published: 2022
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9. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: Thomas U. Ahearn, Haoyu Zhang, Kyriaki Michailidou, Roger L. Milne, Manjeet K. Bolla, Joe Dennis, Alison M. Dunning, Michael Lush, Qin Wang, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Kristan J. Aronson, Paul L. Auer, Annelie Augustinsson, Adinda Baten, Heiko Becher, Sabine Behrens, Javier Benitez, Marina Bermisheva, Carl Blomqvist, Stig E. Bojesen, Bernardo Bonanni, Anne-Lise Børresen-Dale, Hiltrud Brauch, Hermann Brenner, Angela Brooks-Wilson, Thomas Brüning, Barbara Burwinkel, Saundra S. Buys, Federico Canzian, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Georgia Chenevix-Trench, Christine L. Clarke, NBCS Collaborators, J. Margriet Collée, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Peter Devilee, Thilo Dörk, Miriam Dwek, Diana M. Eccles, D. Gareth Evans, Peter A. Fasching, Jonine Figueroa, Giuseppe Floris, Manuela Gago-Dominguez, Susan M. Gapstur, José A. García-Sáenz, Mia M. Gaudet, Graham G. Giles, Mark S. Goldberg, Anna González-Neira, Grethe I. Grenaker Alnæs, Mervi Grip, Pascal Guénel, Christopher A. Haiman, Per Hall, Ute Hamann, Elaine F. Harkness, Bernadette A. M. Heemskerk-Gerritsen, Bernd Holleczek, Antoinette Hollestelle, Maartje J. Hooning, Robert N. Hoover, John L. Hopper, Anthony Howell, ABCTB Investigators, kConFab/AOCS Investigators, Milena Jakimovska, Anna Jakubowska, Esther M. John, Michael E. Jones, Audrey Jung, Rudolf Kaaks, Saila Kauppila, Renske Keeman, Elza Khusnutdinova, Cari M. Kitahara, Yon-Dschun Ko, Stella Koutros, Vessela N. Kristensen, Ute Krüger, Katerina Kubelka-Sabit, Allison W. Kurian, Kyriacos Kyriacou, Diether Lambrechts, Derrick G. Lee, Annika Lindblom, Martha Linet, Jolanta Lissowska, Ana Llaneza, Wing-Yee Lo, Robert J. MacInnis, Arto Mannermaa, Mehdi Manoochehri, Sara Margolin, Maria Elena Martinez, Catriona McLean, Alfons Meindl, Usha Menon, Heli Nevanlinna, William G. Newman, Jesse Nodora, Kenneth Offit, Håkan Olsson, Nick Orr, Tjoung-Won Park-Simon, Alpa V. Patel, Julian Peto, Guillermo Pita, Dijana Plaseska-Karanfilska, Ross Prentice, Kevin Punie, Katri Pylkäs, Paolo Radice, Gad Rennert, Atocha Romero, Thomas Rüdiger, Emmanouil Saloustros, Sarah Sampson, Dale P. Sandler, Elinor J. Sawyer, Rita K. Schmutzler, Minouk J. Schoemaker, Ben Schöttker, Mark E. Sherman, Xiao-Ou Shu, Snezhana Smichkoska, Melissa C. Southey, John J. Spinelli, Anthony J. Swerdlow, Rulla M. Tamimi, William J. Tapper, Jack A. Taylor, Lauren R. Teras, Mary Beth Terry, Diana Torres, Melissa A. Troester, Celine M. Vachon, Carolien H. M. van Deurzen, Elke M. van Veen, Philippe Wagner, Clarice R. Weinberg, Camilla Wendt, Jelle Wesseling, Robert Winqvist, Alicja Wolk, Xiaohong R. Yang, Wei Zheng, Fergus J. Couch, Jacques Simard, Peter Kraft, Douglas F. Easton, Paul D. P. Pharoah, Marjanka K. Schmidt, Montserrat García-Closas, and Nilanjan Chatterjee
Subjects: Breast cancer, Etiologic heterogeneity, Genetic predisposition, Common breast cancer susceptibility variants, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate
Published: 2022
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10. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author: Juliette Coignard, Michael Lush, Jonathan Beesley, Tracy A. O’Mara, Joe Dennis, Jonathan P. Tyrer, Daniel R. Barnes, Lesley McGuffog, Goska Leslie, Manjeet K. Bolla, Muriel A. Adank, Simona Agata, Thomas Ahearn, Kristiina Aittomäki, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Norbert Arnold, Kristan J. Aronson, Banu K. Arun, Annelie Augustinsson, Jacopo Azzollini, Daniel Barrowdale, Caroline Baynes, Heko Becher, Marina Bermisheva, Leslie Bernstein, Katarzyna Białkowska, Carl Blomqvist, Stig E. Bojesen, Bernardo Bonanni, Ake Borg, Hiltrud Brauch, Hermann Brenner, Barbara Burwinkel, Saundra S. Buys, Trinidad Caldés, Maria A. Caligo, Daniele Campa, Brian D. Carter, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Wendy K. Chung, Kathleen B. M. Claes, Christine L. Clarke, GEMO Study Collaborators, EMBRACE Collaborators, J. Margriet Collée, Don M. Conroy, Kamila Czene, Mary B. Daly, Peter Devilee, Orland Diez, Yuan Chun Ding, Susan M. Domchek, Thilo Dörk, Isabel dos-Santos-Silva, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, A. Heather Eliassen, Christoph Engel, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Henrik Flyger, Florentia Fostira, Eitan Friedman, Lin Fritschi, Debra Frost, Manuela Gago-Dominguez, Susan M. Gapstur, Judy Garber, Vanesa Garcia-Barberan, Montserrat García-Closas, José A. García-Sáenz, Mia M. Gaudet, Simon A. Gayther, Andrea Gehrig, Vassilios Georgoulias, Graham G. Giles, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Anna González-Neira, Mark H. Greene, Pascal Guénel, Lothar Haeberle, Eric Hahnen, Christopher A. Haiman, Niclas Håkansson, Per Hall, Ute Hamann, Patricia A. Harrington, Steven N. Hart, Wei He, Frans B. L. Hogervorst, Antoinette Hollestelle, John L. Hopper, Darling J. Horcasitas, Peter J. Hulick, David J. Hunter, Evgeny N. Imyanitov, KConFab Investigators, HEBON Investigators, ABCTB Investigators, Agnes Jager, Anna Jakubowska, Paul A. James, Uffe Birk Jensen, Esther M. John, Michael E. Jones, Rudolf Kaaks, Pooja Middha Kapoor, Beth Y. Karlan, Renske Keeman, Elza Khusnutdinova, Johanna I. Kiiski, Yon-Dschun Ko, Veli-Matti Kosma, Peter Kraft, Allison W. Kurian, Yael Laitman, Diether Lambrechts, Loic Le Marchand, Jenny Lester, Fabienne Lesueur, Tricia Lindstrom, Adria Lopez-Fernández, Jennifer T. Loud, Craig Luccarini, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, John W. M. Martens, Noura Mebirouk, Alfons Meindl, Austin Miller, Roger L. Milne, Marco Montagna, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Finn C. Nielsen, Katie M. O’Brien, Olufunmilayo I. Olopade, Janet E. Olson, Håkan Olsson, Ana Osorio, Laura Ottini, Tjoung-Won Park-Simon, Michael T. Parsons, Inge Sokilde Pedersen, Beth Peshkin, Paolo Peterlongo, Julian Peto, Paul D. P. Pharoah, Kelly-Anne Phillips, Eric C. Polley, Bruce Poppe, Nadege Presneau, Miquel Angel Pujana, Kevin Punie, Paolo Radice, Johanna Rantala, Muhammad U. Rashid, Gad Rennert, Hedy S. Rennert, Mark Robson, Atocha Romero, Maria Rossing, Emmanouil Saloustros, Dale P. Sandler, Regina Santella, Maren T. Scheuner, Marjanka K. Schmidt, Gunnar Schmidt, Christopher Scott, Priyanka Sharma, Penny Soucy, Melissa C. Southey, John J. Spinelli, Zoe Steinsnyder, Jennifer Stone, Dominique Stoppa-Lyonnet, Anthony Swerdlow, Rulla M. Tamimi, William J. Tapper, Jack A. Taylor, Mary Beth Terry, Alex Teulé, Darcy L. Thull, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Alison H. Trainer, Thérèse Truong, Nadine Tung, Celine M. Vachon, Ana Vega, Joseph Vijai, Qin Wang, Barbara Wappenschmidt, Clarice R. Weinberg, Jeffrey N. Weitzel, Camilla Wendt, Alicja Wolk, Siddhartha Yadav, Xiaohong R. Yang, Drakoulis Yannoukakos, Wei Zheng, Argyrios Ziogas, Kristin K. Zorn, Sue K. Park, Mads Thomassen, Kenneth Offit, Rita K. Schmutzler, Fergus J. Couch, Jacques Simard, Georgia Chenevix-Trench, Douglas F. Easton, Nadine Andrieu, and Antonis C. Antoniou
Subjects: Science
Abstract: Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.
Published: 2021
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11. Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Author: Manuel A. Ferreira, Eric R. Gamazon, Fares Al-Ejeh, Kristiina Aittomäki, Irene L. Andrulis, Hoda Anton-Culver, Adalgeir Arason, Volker Arndt, Kristan J. Aronson, Banu K. Arun, Ella Asseryanis, Jacopo Azzollini, Judith Balmaña, Daniel R. Barnes, Daniel Barrowdale, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Katarzyna Białkowska, Carl Blomqvist, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Ake Borg, Hiltrud Brauch, Hermann Brenner, Annegien Broeks, Barbara Burwinkel, Trinidad Caldés, Maria A. Caligo, Daniele Campa, Ian Campbell, Federico Canzian, Jonathan Carter, Brian D. Carter, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Hans Christiansen, Wendy K. Chung, Kathleen B. M. Claes, Christine L. Clarke, EMBRACE Collaborators, GC-HBOC Study Collaborators, GEMO Study Collaborators, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Miguel de la Hoya, Joe Dennis, Peter Devilee, Orland Diez, Thilo Dörk, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, Bent Ejlertsen, Carolina Ellberg, Christoph Engel, Mikael Eriksson, Peter A. Fasching, Olivia Fletcher, Henrik Flyger, Eitan Friedman, Debra Frost, Marike Gabrielson, Manuela Gago-Dominguez, Patricia A. Ganz, Susan M. Gapstur, Judy Garber, Montserrat García-Closas, José A. García-Sáenz, Mia M. Gaudet, Graham G. Giles, Gord Glendon, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Anna González-Neira, Mark H. Greene, Jacek Gronwald, Pascal Guénel, Christopher A. Haiman, Per Hall, Ute Hamann, Wei He, Jane Heyworth, Frans B. L. Hogervorst, Antoinette Hollestelle, Robert N. Hoover, John L. Hopper, Peter J. Hulick, Keith Humphreys, Evgeny N. Imyanitov, ABCTB Investigators, HEBON Investigators, BCFR Investigators, Claudine Isaacs, Milena Jakimovska, Anna Jakubowska, Paul A. James, Ramunas Janavicius, Rachel C. Jankowitz, Esther M. John, Nichola Johnson, Vijai Joseph, Beth Y. Karlan, Elza Khusnutdinova, Johanna I. Kiiski, Yon-Dschun Ko, Michael E. Jones, Irene Konstantopoulou, Vessela N. Kristensen, Yael Laitman, Diether Lambrechts, Conxi Lazaro, Goska Leslie, Jenny Lester, Fabienne Lesueur, Sara Lindström, Jirong Long, Jennifer T. Loud, Jan Lubiński, Enes Makalic, Arto Mannermaa, Mehdi Manoochehri, Sara Margolin, Tabea Maurer, Dimitrios Mavroudis, Lesley McGuffog, Alfons Meindl, Usha Menon, Kyriaki Michailidou, Austin Miller, Marco Montagna, Fernando Moreno, Lidia Moserle, Anna Marie Mulligan, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Ines Nevelsteen, Finn C. Nielsen, Liene Nikitina-Zake, Robert L. Nussbaum, Kenneth Offit, Edith Olah, Olufunmilayo I. Olopade, Håkan Olsson, Ana Osorio, Janos Papp, Tjoung-Won Park-Simon, Michael T. Parsons, Inge Sokilde Pedersen, Ana Peixoto, Paolo Peterlongo, Paul D. P. Pharoah, Dijana Plaseska-Karanfilska, Bruce Poppe, Nadege Presneau, Paolo Radice, Johanna Rantala, Gad Rennert, Harvey A. Risch, Emmanouil Saloustros, Kristin Sanden, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Priyanka Sharma, Xiao-Ou Shu, Jacques Simard, Christian F. Singer, Penny Soucy, Melissa C. Southey, John J. Spinelli, Amanda B. Spurdle, Jennifer Stone, Anthony J. Swerdlow, William J. Tapper, Jack A. Taylor, Manuel R. Teixeira, Mary Beth Terry, Alex Teulé, Mads Thomassen, Kathrin Thöne, Darcy L. Thull, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Thérèse Truong, Nadine Tung, Celine M. Vachon, Christi J. van Asperen, Ans M. W. van den Ouweland, Elizabeth J. van Rensburg, Ana Vega, Alessandra Viel, Qin Wang, Barbara Wappenschmidt, Jeffrey N. Weitzel, Camilla Wendt, Robert Winqvist, Xiaohong R. Yang, Drakoulis Yannoukakos, Argyrios Ziogas, Peter Kraft, Antonis C. Antoniou, Wei Zheng, Douglas F. Easton, Roger L. Milne, Jonathan Beesley, and Georgia Chenevix-Trench
Subjects: Science
Abstract: Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.
Published: 2019
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12. Preoperative Metastatic Brain Tumor-Associated Intracerebral Hemorrhage Is Associated With Dismal Prognosis

Author: Motaz Hamed, Niklas Schäfer, Christian Bode, Valeri Borger, Anna-Laura Potthoff, Lars Eichhorn, Frank A. Giordano, Erdem Güresir, Muriel Heimann, Yon-Dschun Ko, Jennifer Landsberg, Felix Lehmann, Alexander Radbruch, Elisa Scharnböck, Christina Schaub, Katjana S. Schwab, Johannes Weller, Ulrich Herrlinger, Hartmut Vatter, Patrick Schuss, and Matthias Schneider
Subjects: hemorrhage, brain metastases, overall survival, hemorrhagic transformation, cranial surgery, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: ObjectIntra-tumoral hemorrhage is considered an imaging characteristic of advanced cancer disease. However, data on the influence of intra-tumoral hemorrhage in patients with brain metastases (BM) remains scarce. We aimed at investigating patients with BM who underwent neurosurgical resection of the metastatic lesion for a potential impact of preoperative hemorrhagic transformation on overall survival (OS).MethodsBetween 2013 and 2018, 357 patients with BM were surgically treated at the authors’ neuro-oncological center. Preoperative magnetic resonance imaging (MRI) examinations were assessed for the occurrence of malignant hemorrhagic transformation.Results122 of 375 patients (34%) with BM revealed preoperative intra-tumoral hemorrhage. Patients with hemorrhagic transformed BM exhibited a median OS of 5 months compared to 12 months for patients without intra-tumoral hemorrhage. Multivariate analysis revealed preoperative hemorrhagic transformation as an independent and significant predictor for worsened OS.ConclusionsThe present study identifies preoperative intra-tumoral hemorrhage as an indicator variable for poor prognosis in patients with BM undergoing neurosurgical treatment.
Published: 2021
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13. Outcome of Elderly Patients With Surgically Treated Brain Metastases

Author: Muriel Heimann, Niklas Schäfer, Christian Bode, Valeri Borger, Lars Eichhorn, Frank A. Giordano, Erdem Güresir, Andreas H. Jacobs, Yon-Dschun Ko, Jennifer Landsberg, Felix Lehmann, Alexander Radbruch, Christina Schaub, Katjana S. Schwab, Johannes Weller, Ulrich Herrlinger, Hartmut Vatter, Patrick Schuss, and Matthias Schneider
Subjects: geriatric, brain metastasis, frailty, CCI, prognosis, cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: ObjectIn the light of an aging population and ongoing advances in cancer control, the optimal management in geriatric patients with brain metastases (BM) poses an increasing challenge, especially due to the scarce data available. We therefore analyzed our institutional data with regard to factors influencing overall survival (OS) in geriatric patients with BM.MethodsBetween 2013 and 2018, patients aged ≥ 65 years with surgically treated BM were included in this retrospective analysis. In search of preoperatively identifiable risk factors for poor OS, in addition to the underlying cancer, the preoperative frailty of patients was analyzed using the modified Frailty Index (mFI).ResultsA total of 180 geriatric patients with surgically treated BM were identified. Geriatric patients categorized as least-frail achieved a median OS of 18 months, whereas frailest patients achieved an OS of only 3 months (p5 mg/l” (p=0.01) and “frailest patients (mFI ≥ 0.27)” (p=0.002) as predictors for reduced OS in older patients undergoing surgical treatment for BM.ConclusionsIn this retrospective series, pre-operative frailty was associated with poor survival in elderly patients with BM requiring surgery. Our analyses warrant thorough counselling and support of affected elderly patients and their families.
Published: 2021
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14. The Impact of Prolonged Mechanical Ventilation on Overall Survival in Patients With Surgically Treated Brain Metastases

Author: Patrick Schuss, Niklas Schäfer, Christian Bode, Valeri Borger, Lars Eichhorn, Frank A. Giordano, Erdem Güresir, Muriel Heimann, Yon-Dschun Ko, Jennifer Landsberg, Felix Lehmann, Anna-Laura Potthoff, Alexander Radbruch, Christina Schaub, Katjana S. Schwab, Johannes Weller, Hartmut Vatter, Ulrich Herrlinger, and Matthias Schneider
Subjects: prolonged mechanical ventilation, brain metastases, overall survival, cancer, intensive care, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: ObjectiveSurgical resection represents a common treatment modality in patients with brain metastasis (BM). Postoperative prolonged mechanical ventilation (PMV) might have an enormous impact on the overall survival (OS) of these patients suffering from advanced cancer disease. We therefore have analyzed our institutional database with regard to a potential impact of PMV on OS of patients who had undergone surgery for brain metastases.Methods360 patients with surgically treated brain metastases were included. The definition of PMV consisted of postoperative mechanical ventilation lasting for more than 48 hours. Analysis of survival incorporating established prognostic factors such as age, location of BM, and preoperative physical status was performed.Results14 of 360 patients with BM (4%) suffered from postoperative PMV after surgical treatment of BM. Patients with PMV presented in a significantly more impaired neurological condition preoperatively than patients without (p
Published: 2021
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15. Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author: Juliette Coignard, Michael Lush, Jonathan Beesley, Tracy A. O’Mara, Joe Dennis, Jonathan P. Tyrer, Daniel R. Barnes, Lesley McGuffog, Goska Leslie, Manjeet K. Bolla, Muriel A. Adank, Simona Agata, Thomas Ahearn, Kristiina Aittomäki, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Norbert Arnold, Kristan J. Aronson, Banu K. Arun, Annelie Augustinsson, Jacopo Azzollini, Daniel Barrowdale, Caroline Baynes, Heko Becher, Marina Bermisheva, Leslie Bernstein, Katarzyna Białkowska, Carl Blomqvist, Stig E. Bojesen, Bernardo Bonanni, Ake Borg, Hiltrud Brauch, Hermann Brenner, Barbara Burwinkel, Saundra S. Buys, Trinidad Caldés, Maria A. Caligo, Daniele Campa, Brian D. Carter, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Wendy K. Chung, Kathleen B. M. Claes, Christine L. Clarke, GEMO Study Collaborators, EMBRACE Collaborators, J. Margriet Collée, Don M. Conroy, Kamila Czene, Mary B. Daly, Peter Devilee, Orland Diez, Yuan Chun Ding, Susan M. Domchek, Thilo Dörk, Isabel dos-Santos-Silva, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, A. Heather Eliassen, Christoph Engel, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Henrik Flyger, Florentia Fostira, Eitan Friedman, Lin Fritschi, Debra Frost, Manuela Gago-Dominguez, Susan M. Gapstur, Judy Garber, Vanesa Garcia-Barberan, Montserrat García-Closas, José A. García-Sáenz, Mia M. Gaudet, Simon A. Gayther, Andrea Gehrig, Vassilios Georgoulias, Graham G. Giles, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Anna González-Neira, Mark H. Greene, Pascal Guénel, Lothar Haeberle, Eric Hahnen, Christopher A. Haiman, Niclas Håkansson, Per Hall, Ute Hamann, Patricia A. Harrington, Steven N. Hart, Wei He, Frans B. L. Hogervorst, Antoinette Hollestelle, John L. Hopper, Darling J. Horcasitas, Peter J. Hulick, David J. Hunter, Evgeny N. Imyanitov, KConFab Investigators, HEBON Investigators, ABCTB Investigators, Agnes Jager, Anna Jakubowska, Paul A. James, Uffe Birk Jensen, Esther M. John, Michael E. Jones, Rudolf Kaaks, Pooja Middha Kapoor, Beth Y. Karlan, Renske Keeman, Elza Khusnutdinova, Johanna I. Kiiski, Yon-Dschun Ko, Veli-Matti Kosma, Peter Kraft, Allison W. Kurian, Yael Laitman, Diether Lambrechts, Loic Le Marchand, Jenny Lester, Fabienne Lesueur, Tricia Lindstrom, Adria Lopez-Fernández, Jennifer T. Loud, Craig Luccarini, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, John W. M. Martens, Noura Mebirouk, Alfons Meindl, Austin Miller, Roger L. Milne, Marco Montagna, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Finn C. Nielsen, Katie M. O’Brien, Olufunmilayo I. Olopade, Janet E. Olson, Håkan Olsson, Ana Osorio, Laura Ottini, Tjoung-Won Park-Simon, Michael T. Parsons, Inge Sokilde Pedersen, Beth Peshkin, Paolo Peterlongo, Julian Peto, Paul D. P. Pharoah, Kelly-Anne Phillips, Eric C. Polley, Bruce Poppe, Nadege Presneau, Miquel Angel Pujana, Kevin Punie, Paolo Radice, Johanna Rantala, Muhammad U. Rashid, Gad Rennert, Hedy S. Rennert, Mark Robson, Atocha Romero, Maria Rossing, Emmanouil Saloustros, Dale P. Sandler, Regina Santella, Maren T. Scheuner, Marjanka K. Schmidt, Gunnar Schmidt, Christopher Scott, Priyanka Sharma, Penny Soucy, Melissa C. Southey, John J. Spinelli, Zoe Steinsnyder, Jennifer Stone, Dominique Stoppa-Lyonnet, Anthony Swerdlow, Rulla M. Tamimi, William J. Tapper, Jack A. Taylor, Mary Beth Terry, Alex Teulé, Darcy L. Thull, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Alison H. Trainer, Thérèse Truong, Nadine Tung, Celine M. Vachon, Ana Vega, Joseph Vijai, Qin Wang, Barbara Wappenschmidt, Clarice R. Weinberg, Jeffrey N. Weitzel, Camilla Wendt, Alicja Wolk, Siddhartha Yadav, Xiaohong R. Yang, Drakoulis Yannoukakos, Wei Zheng, Argyrios Ziogas, Kristin K. Zorn, Sue K. Park, Mads Thomassen, Kenneth Offit, Rita K. Schmutzler, Fergus J. Couch, Jacques Simard, Georgia Chenevix-Trench, Douglas F. Easton, Nadine Andrieu, and Antonis C. Antoniou
Subjects: Science
Abstract: A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4
Published: 2021
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16. Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): part 1 of an open-label, multicentre, randomised, active-controlled, phase 3 trial

Author: Hartmut Goldschmidt, Elias K Mai, Uta Bertsch, Roland Fenk, Eva Nievergall, Diana Tichy, Britta Besemer, Jan Dürig, Roland Schroers, Ivana von Metzler, Mathias Hänel, Christoph Mann, Anne M Asemissen, Bernhard Heilmeier, Niels Weinhold, Stefanie Huhn, Katharina Kriegsmann, Steffen P Luntz, Tobias A W Holderried, Karolin Trautmann-Grill, Deniz Gezer, Maika Klaiber-Hakimi, Martin Müller, Cyrus Khandanpour, Wolfgang Knauf, Christof Scheid, Markus Munder, Thomas Geer, Hendrik Riesenberg, Jörg Thomalla, Martin Hoffmann, Marc S Raab, Hans J Salwender, Katja C Weisel, Joachim Behringer, Helga Bernhard, Christiane Bernhardt, Igor W Blau, Claus Bolling, Daniel Debatin, Gerrit Dingeldein, Barbara Ferstl, Claudia Fest, Stefan Fronhoffs, Stephan Fuhrmann, Tobias Gaska, Martin Görner, Ullrich Graeven, Jochen Grassinger, Michael Heinsch, Gerhard Held, Olaf Hopfer, Peter Immenschuh, Dominic Kaddu-Mulindwa, Martine Klausmann, Stefan Klein, Yon-Dschun Ko, Georg Köchling, Michael Koenigsmann, Philippe Kostrewa, Doris Maria Kraemer, Stephan Kremers, Martin Kropff, Paul La Rosée, Rolf Mahlberg, Uwe Martens, Michael Neise, Holger Nückel, Wolfram Pönisch, Maria Procaccianti, Mohammed R Rafiyan, Peter Reimer, Armin Riecke, Mathias Rummel, Volker Runde, Markus Schaich, Christoph Scheid, Martin Schmidt-Hieber, Stefan Schmitt, Daniel Schöndube, Andreas Schwarzer, Peter Staib, Heike Steiniger, Dirk Sturmberg, Hans-Joachim Tischler, Arne Trummer, Barbara Tschechne, Walter Verbeek, Bettina Whitlock, Maike de Wit, Matthias Zaiß, and Carsten Ziske
Subjects: Male, Bortezomib, Antineoplastic Combined Chemotherapy Protocols, Medizin, Humans, Female, Induction Chemotherapy, Hematology, Middle Aged, Multiple Myeloma, Lenalidomide, Dexamethasone
Abstract: Anti-CD38 monoclonal antibodies have consistently shown increased efficacy when added to standard of care for patients with multiple myeloma. We aimed to assess the efficacy of isatuximab in addition to lenalidomide, bortezomib, and dexamethasone in patients with newly diagnosed transplantation-eligible multiple myeloma.This open-label, multicentre, randomised, active-controlled, phase 3 trial was done at 67 academic and oncology practice centres in Germany. This study is ongoing and divided into two parts; herein, we report results from part 1. Eligible patients were aged 18-70 years; had a confirmed diagnosis of untreated multiple myeloma requiring systemic treatment and a WHO performance status of 0-2; and were eligible for induction therapy, high-dose melphalan and autologous haematopoietic stem-cell transplantation, and maintenance treatment. Patients were randomly assigned (1:1) to receive three 42-day cycles of induction therapy either with isatuximab plus lenalidomide, bortezomib, and dexamethasone (isatuximab group) or lenalidomide, bortezomib, and dexamethasone alone (control group) using a web-based system and permuted blocks. Patients in both groups received lenalidomide (25 mg orally on days 1-14 and 22-35), bortezomib (1·3 mg/mBetween Oct 23, 2018, and Sep 22, 2020, 660 patients were included in the ITT analysis (331 in the isatuximab group and 329 in the control group). 654 (99%) patients were White, two were African, one was Arabic, and three were Asian. 250 (38%) were women and 410 (62%) were men. The median age was 59 years (IQR 54-64). MRD negativity after induction therapy was reached in 166 (50%) patients in the isatuximab group versus 117 (36%) in the control group (OR 1·82 [95% CI 1·33-2·48]; p=0·00017). Median follow-up time from start to end of induction therapy was 125 days (IQR 125-131) versus 125 days (125-132). At least one grade 3 or 4 adverse event occurred in 208 (63%) of 330 patients versus 199 (61%) of 328 patients. Neutropenia of grade 3 or 4 occurred in 77 (23%) versus 23 (7%) patients and infections of grade 3 or 4 occurred in 40 (12%) versus 32 (10%) patients. Among 12 deaths during induction therapy, one death due to septic shock in the isatuximab group and four deaths (one cardiac decompensation, one hepatic and renal failure, one cardiac arrest, and one drug-induced enteritis) in the control group were considered treatment-related.Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone for induction therapy improved rates of MRD negativity with no new safety signals in patients with newly diagnosed transplantation-eligible multiple myeloma.Sanofi and Bristol Myers Squibb (Celgene).
Published: 2022
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17. Atypische Akromionfraktur nach Sturz eines 18-jährigen Patienten

Author: Jennifer Thaeren, Eugen Muschler, Yon-Dschun Ko, Arnd Winnesberg, and Kai Wilhelm
Published: 2022
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18. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Author: Fergus J. Couch, Karoline B. Kuchenbaecker, Kyriaki Michailidou, Gustavo A. Mendoza-Fandino, Silje Nord, Janna Lilyquist, Curtis Olswold, Emily Hallberg, Simona Agata, Habibul Ahsan, Kristiina Aittomäki, Christine Ambrosone, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Banu K. Arun, Brita Arver, Monica Barile, Rosa B. Barkardottir, Daniel Barrowdale, Lars Beckmann, Matthias W. Beckmann, Javier Benitez, Stephanie V. Blank, Carl Blomqvist, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Bernardo Bonanni, Hiltrud Brauch, Hermann Brenner, Barbara Burwinkel, Saundra S. Buys, Trinidad Caldes, Maria A. Caligo, Federico Canzian, Jane Carpenter, Jenny Chang-Claude, Stephen J. Chanock, Wendy K. Chung, Kathleen B. M. Claes, Angela Cox, Simon S. Cross, Julie M. Cunningham, Kamila Czene, Mary B. Daly, Francesca Damiola, Hatef Darabi, Miguel de la Hoya, Peter Devilee, Orland Diez, Yuan C. Ding, Riccardo Dolcetti, Susan M. Domchek, Cecilia M. Dorfling, Isabel dos-Santos-Silva, Martine Dumont, Alison M. Dunning, Diana M. Eccles, Hans Ehrencrona, Arif B. Ekici, Heather Eliassen, Steve Ellis, Peter A. Fasching, Jonine Figueroa, Dieter Flesch-Janys, Asta Försti, Florentia Fostira, William D. Foulkes, Tara Friebel, Eitan Friedman, Debra Frost, Marike Gabrielson, Marilie D. Gammon, Patricia A. Ganz, Susan M. Gapstur, Judy Garber, Mia M. Gaudet, Simon A. Gayther, Anne-Marie Gerdes, Maya Ghoussaini, Graham G. Giles, Gord Glendon, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Anna González-Neira, Mark H. Greene, Jacek Gronwald, Pascal Guénel, Marc Gunter, Lothar Haeberle, Christopher A. Haiman, Ute Hamann, Thomas V. O. Hansen, Steven Hart, Sue Healey, Tuomas Heikkinen, Brian E. Henderson, Josef Herzog, Frans B. L. Hogervorst, Antoinette Hollestelle, Maartje J. Hooning, Robert N. Hoover, John L. Hopper, Keith Humphreys, David J. Hunter, Tomasz Huzarski, Evgeny N. Imyanitov, Claudine Isaacs, Anna Jakubowska, Paul James, Ramunas Janavicius, Uffe Birk Jensen, Esther M. John, Michael Jones, Maria Kabisch, Siddhartha Kar, Beth Y. Karlan, Sofia Khan, Kay-Tee Khaw, Muhammad G. Kibriya, Julia A. Knight, Yon-Dschun Ko, Irene Konstantopoulou, Veli-Matti Kosma, Vessela Kristensen, Ava Kwong, Yael Laitman, Diether Lambrechts, Conxi Lazaro, Eunjung Lee, Loic Le Marchand, Jenny Lester, Annika Lindblom, Noralane Lindor, Sara Lindstrom, Jianjun Liu, Jirong Long, Jan Lubinski, Phuong L. Mai, Enes Makalic, Kathleen E. Malone, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, Frederik Marme, John W. M. Martens, Lesley McGuffog, Alfons Meindl, Austin Miller, Roger L. Milne, Penelope Miron, Marco Montagna, Sylvie Mazoyer, Anna M. Mulligan, Taru A. Muranen, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Børge G. Nordestgaard, Robert L. Nussbaum, Kenneth Offit, Edith Olah, Olufunmilayo I. Olopade, Janet E. Olson, Ana Osorio, Sue K. Park, Petra H. Peeters, Bernard Peissel, Paolo Peterlongo, Julian Peto, Catherine M. Phelan, Robert Pilarski, Bruce Poppe, Katri Pylkäs, Paolo Radice, Nazneen Rahman, Johanna Rantala, Christine Rappaport, Gad Rennert, Andrea Richardson, Mark Robson, Isabelle Romieu, Anja Rudolph, Emiel J. Rutgers, Maria-Jose Sanchez, Regina M. Santella, Elinor J. Sawyer, Daniel F. Schmidt, Marjanka K. Schmidt, Rita K. Schmutzler, Fredrick Schumacher, Rodney Scott, Leigha Senter, Priyanka Sharma, Jacques Simard, Christian F. Singer, Olga M. Sinilnikova, Penny Soucy, Melissa Southey, Doris Steinemann, Marie Stenmark-Askmalm, Dominique Stoppa-Lyonnet, Anthony Swerdlow, Csilla I. Szabo, Rulla Tamimi, William Tapper, Manuel R. Teixeira, Soo-Hwang Teo, Mary B. Terry, Mads Thomassen, Deborah Thompson, Laima Tihomirova, Amanda E. Toland, Robert A. E. M. Tollenaar, Ian Tomlinson, Thérèse Truong, Helen Tsimiklis, Alex Teulé, Rosario Tumino, Nadine Tung, Clare Turnbull, Giski Ursin, Carolien H. M. van Deurzen, Elizabeth J. van Rensburg, Raymonda Varon-Mateeva, Zhaoming Wang, Shan Wang-Gohrke, Elisabete Weiderpass, Jeffrey N. Weitzel, Alice Whittemore, Hans Wildiers, Robert Winqvist, Xiaohong R. Yang, Drakoulis Yannoukakos, Song Yao, M Pilar Zamora, Wei Zheng, Per Hall, Peter Kraft, Celine Vachon, Susan Slager, Georgia Chenevix-Trench, Paul D. P. Pharoah, Alvaro A. N. Monteiro, Montserrat García-Closas, Douglas F. Easton, and Antonis C. Antoniou
Subjects: Science
Abstract: Oestrogen negative breast cancer is associated with a poor prognosis. In this study, the authors perform a meta-analysis of 11 breast cancer genome-wide association studies and identify four new loci associated with oestrogen negative breast cancer risk. These findings may aid in stratifying patients in the clinic.
Published: 2016
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19. Developing content-valid tumor-specific PRO-CTCAE item sets: analysis of a cross-sectional survey in three German outpatient cancer centers

Author: Maximilian Günther, Leopold Hentschel, Markus Schuler, Theresa Müller, Katharina Schütte, Yon-Dschun Ko, Ingo Schmidt-Wolf, and Ulrich Jaehde
Abstract: Background To include the patient perspective in the assessment of adverse events (AE) in oncology, a patient-reported outcomes (PRO) version of the Common Terminology Criteria for Adverse Events (CTCAE) was developed by the NCI, the so called PRO-CTCAE. The objective of this study was the development of disease-specific PRO-CTCAE item sets with high content validity for patients with breast cancer (BC), multiple myeloma (MM) and prostate cancer (PC). Methods A cross-sectional survey was conducted at three German outpatient cancer centers. Prevalence and importance of the 78 PRO-CTCAE symptoms were assessed using a patient questionnaire. To select the most relevant PRO-CTCAE items for each tumor entity, symptoms were ranked based on patient answers. Results 101 patients with BC, 107 with MM, and 66 with PC participated. The final item sets contained 21 symptoms (BC) or 19 symptoms (MM and PC), respectively. Eight symptoms were represented in all three item sets. Fatigue was the symptom with the highest ranking across item sets followed by sleep disorders. Symptoms with the highest rankings represented in only one item set were symptoms affecting the urogenital system in the PC item set, blurred vision in the BC item set and appetite loss in the MM item set. Conclusions Individual PRO-CTCAE item sets with high content validity were developed for three tumor diseases on the basis of patient-reported symptom patterns and perceptions. The quality and psychometric criteria of the newly compiled item sets should be further validated.
Published: 2023
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20. Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (Isa-KRd) in Patients with High-Risk Newly Diagnosed Multiple Myeloma: Planned Interim Analysis of the GMMG-Concept Trial

Author: Katja Weisel, Britta Besemer, Mathias Haenel, Raphael Lutz, Christoph Mann, Markus Munder, Martin Goerner, Hans Christian Reinhardt, Axel Nogai, Yon-Dschun Ko, Maike De Wit, Hans Salwender, Christoph Scheid, Ullrich Graeven, Rudolf Peceny, Peter Staib, Annette Dieing, Anna Jauch, Manola Zago, Axel Benner, Diana Tichy, Carsten Bokemeyer, Hartmut Goldschmidt, and Lisa B. Leypoldt
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Published: 2022
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21. Supplement from Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non–Small Cell Lung Carcinoma (NSCLC)

Author: Jürgen Wolf, Reinhard Büttner, Mathieu Clement-Ziza, Lukas C. Heukamp, Britta Kaminsky, Thomas Geist, Ulrich Gerigk, Yon-Dschun Ko, Monika Serke, Carina Heydt, Jana Fassunke, Anna Eisert, Rieke Fischer, Sebastian Michels, Katharina König, Frank Ueckeroth, Michael Rauer, Anna Kron, Michaela A. Ihle, Sabine Merkelbach-Bruse, Matthias Scheffler, and Rieke Frank
Abstract: Supplemental Table 1-7 Supplemental Table 1: Diagnostic panels used for Next-generation sequencing (NGS) Supplemental Table 2: KEAP1 mutations Supplemental Table 3: NFE2L2 mutations Supplemental Table 4: Co-aberrations of KEAP1 Supplemental Table 5: Co-aberrations of NFE2L2 Supplemental Table 6: Distribution on FISH finding depending on histology Supplemental Table 7: Therapeutic outcome of patients receiving systemic therapy.
Published: 2023
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22. Supplementary Data from A Novel Polymorphism in the Promoter Region of ERBB4 Is Associated with Breast and Colorectal Cancer Risk

Author: Hiltrud Brauch, Damjan Glavač, Yon-Dschun Ko, Ute Hamann, Thomas Illig, Caren Vollmert, Hans-Peter Fischer, Susanne Haas, Monica Adina Istrate, Werner Schroth, Christina Justenhoven, and Matjaž Rokavec
Abstract: Supplementary Data from A Novel Polymorphism in the Promoter Region of ERBB4 Is Associated with Breast and Colorectal Cancer Risk
Published: 2023
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23. Data from Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non–Small Cell Lung Carcinoma (NSCLC)

Author: Jürgen Wolf, Reinhard Büttner, Mathieu Clement-Ziza, Lukas C. Heukamp, Britta Kaminsky, Thomas Geist, Ulrich Gerigk, Yon-Dschun Ko, Monika Serke, Carina Heydt, Jana Fassunke, Anna Eisert, Rieke Fischer, Sebastian Michels, Katharina König, Frank Ueckeroth, Michael Rauer, Anna Kron, Michaela A. Ihle, Sabine Merkelbach-Bruse, Matthias Scheffler, and Rieke Frank
Abstract: Purpose: KEAP1 and NFE2L2 mutations are associated with impaired prognosis in a variety of cancers and with squamous cell carcinoma formation in non–small cell lung cancer (NSCLC). However, little is known about frequency, histology dependence, molecular and clinical presentation as well as response to systemic treatment in NSCLC.Experimental Design: Tumor tissue of 1,391 patients with NSCLC was analyzed using next-generation sequencing (NGS). Clinical and pathologic characteristics, survival, and treatment outcome of patients with KEAP1 or NFE2L2 mutations were assessed.Results: KEAP1 mutations occurred with a frequency of 11.3% (n = 157) and NFE2L2 mutations with a frequency of 3.5% (n = 49) in NSCLC patients. In the vast majority of patients, both mutations did not occur simultaneously. KEAP1 mutations were found mainly in adenocarcinoma (AD; 72%), while NFE2L2 mutations were more common in squamous cell carcinoma (LSCC; 59%). KEAP1 mutations were spread over the whole protein, whereas NFE2L2 mutations were clustered in specific hotspot regions. In over 80% of the patients both mutations co-occurred with other cancer-related mutations, among them also targetable aberrations like activating EGFR mutations or MET amplification. Both patient groups showed different patterns of metastases, stage distribution and performance state. No patient with KEAP1 mutation had a response on systemic treatment in first-, second-, or third-line setting. Of NFE2L2-mutated patients, none responded to second- or third-line therapy.Conclusions: KEAP1- and NFE2L2-mutated NSCLC patients represent a highly heterogeneous patient cohort. Both are associated with different histologies and usually are found together with other cancer-related, partly targetable, genetic aberrations. In addition, both markers seem to be predictive for chemotherapy resistance. Clin Cancer Res; 24(13); 3087–96. ©2018 AACR.
Published: 2023
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24. Supplemental Table 8 from Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non–Small Cell Lung Carcinoma (NSCLC)

Author: Jürgen Wolf, Reinhard Büttner, Mathieu Clement-Ziza, Lukas C. Heukamp, Britta Kaminsky, Thomas Geist, Ulrich Gerigk, Yon-Dschun Ko, Monika Serke, Carina Heydt, Jana Fassunke, Anna Eisert, Rieke Fischer, Sebastian Michels, Katharina König, Frank Ueckeroth, Michael Rauer, Anna Kron, Michaela A. Ihle, Sabine Merkelbach-Bruse, Matthias Scheffler, and Rieke Frank
Abstract: Main characteristics of the control group.
Published: 2023
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25. Data from A Novel Polymorphism in the Promoter Region of ERBB4 Is Associated with Breast and Colorectal Cancer Risk

Author: Hiltrud Brauch, Damjan Glavač, Yon-Dschun Ko, Ute Hamann, Thomas Illig, Caren Vollmert, Hans-Peter Fischer, Susanne Haas, Monica Adina Istrate, Werner Schroth, Christina Justenhoven, and Matjaž Rokavec
Abstract: Purpose: The receptor tyrosine kinase ERBB4/HER4 plays a role in cell division, migration, differentiation, as well as apoptosis, and is frequently overexpressed in breast and colorectal tumors. To understand the role of genetic variations in the regulation of ERBB4 expression, we identified new polymorphisms and investigated their functional implication and risk association with breast and colorectal cancer.Experimental Design: We screened colorectal tumors from 92 patients for genetic variants at the ERBB4 ATG −1000 bp 5′-regulatory region by denaturing high-performance liquid chromatography and sequencing. Variants were subjected to DNA-protein interaction analyses (electrophoretic mobility shift assay), reporter gene assays in breast cancer cell lines MDA134 and MDA157, and immunohistochemical analyses of breast tumors. We established genotype frequencies within a breast cancer case-control collection (1,021 cases, 1,015 population-based controls) and a colorectal cancer case-control collection (459 cases, 569 blood donors) using matrix-assisted laser desorption ionization/time of flight mass spectrometry. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were assessed by multivariate logistic regression.Results: We identified five new germ line variants −815 A>T, −782 G>T, −638 insTC, −267 C>G, and −219 del10bp. Two variants showed in vitro functional effects. The −782T allele showed lower protein binding affinity and lower promoter activity compared with the −782G allele, however, the −815T allele showed higher protein binding affinity and higher promoter activity. The −782T variant was identified as a risk allele for breast and colorectal cancer (OR, 1.59; 95% CI, 1.06-2.34 and OR, 2.21; 95% CI, 1.22-3.99, respectively).Conclusion: The ERBB4 −782 G>T polymorphism, by virtue of its in vitro functional implication and incidence, is a risk factor for breast and colorectal cancer.
Published: 2023
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26. Supplementary Tables 1-13 from 19p13.1 Is a Triple-Negative–Specific Breast Cancer Susceptibility Locus

Author: Fergus J. Couch, Douglas F. Easton, Ylermi Soini, Jaana M. Hartikainen, Veli-Matti Kosma, Arto Mannermaa, Xiaoqing Chen, Jonathan Beesley, Georgia Chenevix-Trench, Marie-Rose Christiaens, Anne-Sophie Dieudonne, Sigrid Hatse, Diether Lambrechts, Monica Barile, Siranoush Manoukian, Paolo Peterlongo, Paolo Radice, Janet E. Olson, Susan Slager, V.S. Pankratz, Matthew L. Kosel, Gianluca Severi, Catriona A. McLean, Laura Baglietto, Graham G. Giles, Anne-Lise Børresen-Dale, Vessela Kristensen, Grethe Grenaker Alnæs, Alexander Miron, Esther M. John, Mervi Grip, Arja Jukkola-Vuorinen, Katri Pylkäs, Robert Winqvist, Anna Marie Mulligan, Gord Glendon, Julia A. Knight, Irene L. Andrulis, Maartje J. Hooning, Rob A.E.M. Tollenaar, Caroline Seynaeve, Peter Devilee, Jolanta Lissowska, Mark E. Sherman, Jonine D. Figueroa, Montserrat Garcia-Closas, Diana M. Eccles, Helena Hwang, Foluso Ademuyiwa, Christine B. Ambrosone, Kamila Czene, Per Hall, Malcom W. Reed, Simon S. Cross, Angela Cox, Qin Wang, Manjeet K. Humphreys, Alison M. Dunning, Paul P. Pharoah, Hans Ulrich Ulmer, Thomas Rüdiger, Thomas Dünnebier, Ute Hamann, Chia-Ni Hsiung, Huan-Ming Hsu, Jyh-Cherng Yu, Chen-Yang Shen, Christina Clarke Dur, Leslie Bernstein, Argyrios Ziogas, Hoda Anton-Culver, Minouk J. Schoemaker, Nicholas Orr, Alan Ashworth, Anthony J. Swerdlow, Melissa C. Southey, Daniel J. Park, Carmel Apicella, John L. Hopper, Efraim H. Rosenberg, Linde M. Braaf, Annegien Broeks, Marjanka K. Schmidt, Surapon Wiangnon, Puttisak Puttawibul, Kenneth Muir, Artitaya Lophatananon, Arif B. Ekici, Arndt Hartmann, Matthias W. Beckmann, Peter A. Fasching, Isabel dos Santos Silva, Olivia Fletcher, Nichola Johnson, Julian Peto, Michael J. Kerin, Ian Tomlinson, Elinor Sawyer, Christof Sohn, Andreas Schneeweiss, Frederick Marmé, Barbara Burwinkel, Emilie Cordina-Duverger, Florence Menegaux, Thérèse Truong, Pascal Guénel, Henrik Flyger, Børge G. Nordestgaard, Sune F. Nielsen, Stig E. Bojesen, José Ignacio Arias Pérez, María Pilar Zamora, Javier Benítez, Roger L. Milne, Annie Perkins, Miriam Dwek, Ruth Swann, Helen J. Gogas, George Fountzilas, Alexandra Stavropoulou, Drakoulis Yannoukakos, Penelope Miron, Christa Stegmaier, Volker Arndt, Heiko Müller, Hermann Brenner, Priyanka Sharma, Harsh B. Pathak, JoEllen Weaver, Andrew K. Godwin, Christoph Engel, Sarah Schott, Claus R. Bartram, Alfons Meindl, Rita K. Schmutzler, Hans-Peter Fischer, Yon-Dschun Ko, Hiltrud Brauch, Stefan Nickels, Shan Wang-Gohrke, Hans-Peter Sinn, Dieter Flesch-Janys, Alina Vrieling, Jenny Chang-Claude, Carl Blomqvist, Kristiina Aittomäki, Dario Greco, Heli Nevanlinna, Annika Lindblom, Sara Margolin, Xianshu Wang, Celine M. Vachon, Zachary Fredericksen, and Kristen N. Stevens
Abstract: PDF file - 272K
Published: 2023
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27. Supplementary Materials and Methods, Tables 1-5 from Common Breast Cancer Susceptibility Loci Are Associated with Triple-Negative Breast Cancer

Author: Fergus J. Couch, Xianshu Wang, Heli Nevanlinna, Drakoulis Yannoukakos, Jenny Chang-Claude, Douglas F. Easton, Paul Pharoah, Ute Hamann, Gianluca Severi, Isabel dos Santos Silva, Diether Lambrechts, Grant W. Montgomery, Nicholas G. Martin, Arto Mannermaa, Sara Margolin, Sarah-Jane Dawson, Fiona M. Blows, Jianjun Liu, Astrid Irwanto, Carl Blomqvist, Dario Greco, Jonathan Beesley, Veli-Matti Kosma, Ian Tomlinson, Senno Verhoef, Laura Baglietto, Graham G. Giles, Olivia Fletcher, Julian Peto, Hilde Janssen, Erik Van Limbergen, Yon-Dschun Ko, Arja Jukkola-Vuorinen, Katri Pylkäs, Swati Kulkarni, Foluso Ademuyiwa, Thomas Dünnebier, Asta Försti, Thomas Rüdiger, JoEllen Weaver, Eric Ross, Harsh Pathak, Robert B. Diasio, Zachary Fredericksen, Janet E. Olson, Rosemary Balleine, Christine L. Clarke, George Fountzilas, Athanasios M. Dimopoulos, Dimitrios Pectasides, Florentia Fostira, Irene Konstantopoulou, Hans-Peter Sinn, Judith Heinz, Dieter Flesch-Janys, Stephan Nickels, Rebecca Hein, Nikki Graham, Lorraine Durcan, Susan M. Gerty, William J. Tapper, Arif B. Ekici, Rüdiger Schulz-Wendtland, Matthias W. Beckmann, Arndt Hartmann, Elinor Sawyer, Simon S. Cross, Angela Cox, Marjanka K. Schmidt, Hiltrud Brauch, Robert Winqvist, Christine Ambrosone, Andrew K. Godwin, Jane E. Carpenter, Diana Eccles, Penelope Miron, Peter A. Fasching, Curtis Olswold, Timothy Lesnick, Susan Slager, Adam M. Lee, Celine M. Vachon, and Kristen N. Stevens
Abstract: PDDF file - 167K
Published: 2023
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28. Isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in front-line treatment of high-risk multiple myeloma: interim analysis of the GMMG-CONCEPT trial

Author: Lisa B. Leypoldt, Markus Munder, Anne Marie Asemissen, Hartmut Goldschmidt, Carsten Bokemeyer, Raphael Lutz, Ullrich Graeven, Axel Benner, Britta Besemer, Rudolf Peceny, Manola Zago, Martin Görner, Mathias Hänel, Hans Salwender, Christoph Mann, Katja Weisel, Diana Tichy, Peter Staib, Yon-Dschun Ko, Anna Jauch, Hans Christian Reinhardt, and Igor Wolfgang Blau
Subjects: Oncology, Isatuximab, Myeloma, Phase II trials, Cancer Research, medicine.medical_specialty, business.industry, Medizin, Front line, Hematology, medicine.disease, Interim analysis, Carfilzomib, chemistry.chemical_compound, chemistry, Internal medicine, medicine, business, Multiple myeloma, Dexamethasone, Lenalidomide, medicine.drug
Published: 2021
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29. Multidisciplinary Postoperative Validation of 18F-FDG PET/CT Scan in Nodal Staging of Resected Non-Small Cell Lung Cancer

Author: Benedetta Bedetti, Philipp Schnorr, Sarah May, Jürgen Ruhlmann, Hojjat Ahmadzadehfar, Markus Essler, Alexander Quaas, Reinhard Büttner, Joachim Schmidt, Holger Palmedo, Yon-Dschun Ko, and Kai Wilhelm
Subjects: PET/CT scan, nodal staging, lymph node metastases, non-small cell lung cancer, General Medicine
Abstract: Background: The aim of this study was to examine the validity of PET/CT scans in the preoperative identification of lymph node metastases (LNM) and compare them with postoperative outcomes. Methods: In this retrospective study, we included 87 patients with a solitary lung nodule or biopsy-proven non-small cell lung cancer treated in our institution from 2009 to 2015. Patients were divided into two groups and four subgroups, depending on pre- and postoperative findings. Results: According to our analysis, PET/CT scan has a sensitivity of 50%, a specificity of 88.89%, a positive predictive value of 63.16%, and a negative predictive value of 82.35%. Among the patients, 13.8% were downstaged in PET-CT, while 8% were upstaged. In 78.2% of cases, the PET/CT evaluation was consistent with the histology. Metastases without extracapsular invasion were seldom recognized on PET/CT. Conclusions: This analysis showed the significance of extracapsular tumor invasion, which causes an inflammatory reaction, on LNM, which is probably responsible for preoperative false-positive findings. In conclusion, PET/CT scans are very effective in identifying patients without tumors. Furthermore, it is highly probable that patients with negative findings are free of disease.
Published: 2022
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30. Quantum Cascade Laser-Based Infrared Imaging as a Label-Free and Automated Approach to Determine Mutations in Lung Adenocarcinoma

Author: Jana Fassunke, Klaus Gerwert, Frederik Großerueschkamp, Reinhard Buettner, Nina Goertzen, Yon-Dschun Ko, Joachim Schmidt, Roberto Pappesch, and Thomas Brüning
Subjects: Male, Pathology, medicine.medical_specialty, Lung Neoplasms, DNA Mutational Analysis, Adenocarcinoma of Lung, medicine.disease_cause, Sensitivity and Specificity, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Spectroscopy, Fourier Transform Infrared, medicine, Humans, Typing, Lung cancer, Aged, 030304 developmental biology, Aged, 80 and over, Microscopy, 0303 health sciences, Mutation, Oncogene, business.industry, Middle Aged, medicine.disease, Molecular diagnostics, 030220 oncology & carcinogenesis, Adenocarcinoma, Immunohistochemistry, Female, KRAS, Lasers, Semiconductor, business
Abstract: Therapeutic decisions in lung cancer critically depend on the determination of histologic types and oncogene mutations. Therefore, tumor samples are subjected to standard histologic and immunohistochemical analyses and examined for relevant mutations using comprehensive molecular diagnostics. In this study, an alternative diagnostic approach for automatic and label-free detection of mutations in lung adenocarcinoma tissue using quantum cascade laser-based infrared imaging is presented. For this purpose, a five-step supervised classification algorithm was developed, which was not only able to detect tissue types and tumor lesions, but also the tumor type and mutation status of adenocarcinomas. Tumor detection was verified on a data set of 214 patient samples with a specificity of 97% and a sensitivity of 95%. Furthermore, histology typing was verified on samples from 203 of the 214 patients with a specificity of 97% and a sensitivity of 94% for adenocarcinoma. The most frequently occurring mutations in adenocarcinoma (KRAS, EGFR, and TP53) were differentiated by this technique. Detection of mutations was verified in 60 patient samples from the data set with a sensitivity and specificity of 95% for each mutation. This demonstrates that quantum cascade laser infrared imaging can be used to analyze morphologic differences as well as molecular changes. Therefore, this single, one-step measurement provides comprehensive diagnostics of lung cancer histology types and most frequent mutations.
Published: 2021
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31. DNA methylation biomarkers for noninvasive detection of triple-negative breast cancer using liquid biopsy

Author: Mehdi Manoochehri, Nasim Borhani, Clarissa Gerhäuser, Yassen Assenov, Maximilian Schönung, Thomas Hielscher, Brock C. Christensen, Min Kyung Lee, Hermann‐Josef Gröne, Daniel B. Lipka, Thomas Brüning, Hiltrud Brauch, Yon‐Dschun Ko, and Ute Hamann
Subjects: Genetic Markers, Cancer Research, Oncology, Tumor Suppressor Proteins, Biomarkers, Tumor, Liquid Biopsy, Humans, Triple Negative Breast Neoplasms, DNA, DNA Methylation, Cell-Free Nucleic Acids, Microtubule-Associated Proteins, Transcription Factors
Abstract: Noninvasive detection of aberrant DNA methylation could provide invaluable biomarkers for earlier detection of triple-negative breast cancer (TNBC) which could help clinicians with easier and more efficient treatment options. We evaluated genome-wide DNA methylation data derived from TNBC and normal breast tissues, peripheral blood of TNBC cases and controls and reference samples of sorted blood and mammary cells. Differentially methylated regions (DMRs) between TNBC and normal breast tissues were stringently selected, verified and externally validated. A machine-learning algorithm was applied to select the top DMRs, which then were evaluated on plasma-derived circulating cell-free DNA (cfDNA) samples of TNBC patients and healthy controls. We identified 23 DMRs accounting for the methylation profile of blood cells and reference mammary cells and then selected six top DMRs for cfDNA analysis. We quantified un-/methylated copies of these DMRs by droplet digital PCR analysis in a plasma test set from TNBC patients and healthy controls and confirmed our findings obtained on tissues. Differential cfDNA methylation was confirmed in an independent validation set of plasma samples. A methylation score combining signatures of the top three DMRs overlapping with the SPAG6, LINC10606 and TBCD/ZNF750 genes had the best capability to discriminate TNBC patients from controls (AUC = 0.78 in the test set and AUC = 0.74 in validation set). Our findings demonstrate the usefulness of cfDNA-based methylation signatures as noninvasive liquid biopsy markers for the diagnosis of TNBC.
Published: 2022

32. [Atypical acromion fracture after fall of an 18-year-old patient]

Author: Jennifer, Thaeren, Eugen, Muschler, Yon-Dschun, Ko, Arnd, Winnesberg, and Kai, Wilhelm
Subjects: Fractures, Bone, Fracture Fixation, Internal, Adolescent, Humans, Acromion
Published: 2022

33. Plasma Proteomics Enable Differentiation of Lung Adenocarcinoma from Chronic Obstructive Pulmonary Disease (COPD)

Author: Thilo Bracht, Daniel Kleefisch, Karin Schork, Kathrin E. Witzke, Weiqiang Chen, Malte Bayer, Jan Hovanec, Georg Johnen, Swetlana Meier, Yon-Dschun Ko, Thomas Behrens, Thomas Brüning, Jana Fassunke, Reinhard Buettner, Julian Uszkoreit, Michael Adamzik, Martin Eisenacher, and Barbara Sitek
Subjects: Proteomics, Lung Neoplasms, Organic Chemistry, lung cancer, plasma proteomics, machine learning, artificial intelligence, random forest, Ig kappa light chain, SERPINA3, SAA1, Adenocarcinoma of Lung, General Medicine, Catalysis, Computer Science Applications, Inorganic Chemistry, Pulmonary Disease, Chronic Obstructive, Humans, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Biomarkers
Abstract: Chronic obstructive pulmonary disease (COPD) is a major risk factor for the development of lung adenocarcinoma (AC). AC often develops on underlying COPD; thus, the differentiation of both entities by biomarker is challenging. Although survival of AC patients strongly depends on early diagnosis, a biomarker panel for AC detection and differentiation from COPD is still missing. Plasma samples from 176 patients with AC with or without underlying COPD, COPD patients, and hospital controls were analyzed using mass-spectrometry-based proteomics. We performed univariate statistics and additionally evaluated machine learning algorithms regarding the differentiation of AC vs. COPD and AC with COPD vs. COPD. Univariate statistics revealed significantly regulated proteins that were significantly regulated between the patient groups. Furthermore, random forest classification yielded the best performance for differentiation of AC vs. COPD (area under the curve (AUC) 0.935) and AC with COPD vs. COPD (AUC 0.916). The most influential proteins were identified by permutation feature importance and compared to those identified by univariate testing. We demonstrate the great potential of machine learning for differentiation of highly similar disease entities and present a panel of biomarker candidates that should be considered for the development of a future biomarker panel.
Published: 2022

34. Die Rolle der Systemtherapie bei Lungenmetastasen mit Lymphknotenbefall

Author: Yon-Dschun Ko
Subjects: Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, 030228 respiratory system, business.industry, Medicine public health, medicine, 030208 emergency & critical care medicine, business
Abstract: Die moderne Systemtherapie mit Chemotherapie, zielgerichteter Therapie und Immuntherapie hat bei vielen Tumorerkrankungen in den letzten 15 Jahren zu einer deutlichen Verbesserung des Gesamtuberlebens gefuhrt. Somit ist die operative Therapie von Lungenmetastasen und Lymphknotenmetastasen nicht nur wertvoll, um eine Heilung bei ausgesuchten Tumoren zu erreichen, sondern sie kann und muss eingesetzt werden, um im Falle einer umschriebenen Progredienz Spitzen des Tumorwachstums zu eliminieren. Diese konnen Ausdruck einer Tumorheterogenitat sein, die von der Systemtherapie nicht erreicht werden. Abhangig von der Dynamik und der Ausdehnung der Metastasierung muss das therapeutische Vorgehen individuell im Tumorboard entschieden werden.
Published: 2020
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35. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

Author: Ana Peixoto, Ian Tomlinson, Thérèse Truong, Amanda E. Toland, Anna Marie Mulligan, Michael Untch, Susan J. Ramus, Kenneth Offit, John J. Spinelli, Clarice R. Weinberg, Kyriaki Michailidou, Javier Benitez, Rita K. Schmutzler, Lizet E. van der Kolk, Heli Nevanlinna, Annika Lindblom, Sara Margolin, Stella Koutros, Elza Khusnutdinova, Diana Eccles, Lenka Foretova, Wolfgang Janni, Jennifer T. Loud, Roger L. Milne, Patrick Neven, Thomas U. Ahearn, Hedy S. Rennert, Karolina Prajzendanc, Melissa C. Southey, Ramunas Janavicius, Finn Cilius Nielsen, Pascal Guénel, Antoinette Hollestelle, Jolanta Lissowska, Ni Zhao, Melissa Christiaens, Hoda Anton-Culver, Ans M.W. van den Ouweland, Christopher A. Haiman, Debra Frost, Vessela N. Kristensen, Bernard Peissel, Muhammad Usman Rashid, Noura Mebirouk, Claudine Isaacs, Matthias W. Beckmann, Sofia Khan, Xia Jiang, Jack A. Taylor, Peter Hillemanns, Robert Winqvist, Susan L. Neuhausen, Marina Bermisheva, Alicja Wolk, Katherine L. Nathanson, Judy Garber, Siranoush Manoukian, Simon S. Cross, Flavio Lejbkowicz, Manjeet K. Bolla, Goska Leslie, Saundra S. Buys, Banu Arun, Xiaohong R. Yang, Peter Schürmann, Irene Konstantopoulou, Mia M. Gaudet, Rob A. E. M. Tollenaar, Joe Dennis, Louise Izatt, David E. Goldgar, Anna Jakubowska, Alicja Lukomska, Fabienne Lesueur, Susanna C. Larsson, Peter Devilee, Helen Byers, Bernd Holleczek, Marc Tischkowitz, Arif B. Ekici, Austin Miller, Carl Blomqvist, Christopher R. Hake, Paul D.P. Pharoah, Harvey A. Risch, Kristin K. Zorn, Mehdi Manoochehri, Kamila Czene, Peter A. Fasching, Trinidad Caldés, Hanna Huebner, Agnes Jager, William G. Newman, Lesley McGuffog, Maren T. Scheuner, Nick Orr, Susan M. Domchek, Antonis C. Antoniou, Peter Kraft, Pooja Middha Kapoor, Daniel R. Barnes, Christine L. Clarke, Douglas F. Easton, Bernadette A M Heemskerk-Gerritsen, Ross L. Prentice, Mark E. Sherman, Elizabeth J. van Rensburg, Michael Jones, Åke Borg, Diether Lambrechts, Mark H. Greene, Mark S. Goldberg, Peter J. Hulick, Maria Elena Martinez, Arto Mannermaa, Frans B. L. Hogervorst, Christian F. Singer, Johanna Rantala, Esther M. John, Jesse Nodora, Wendy K. Chung, Csilla Szabo, Mads Thomassen, Tracy A. O'Mara, Kelly-Anne Phillips, Manuela Gago-Dominguez, Jacques Simard, John L. Hopper, Jacopo Azzollini, Rudolf Kaaks, Haoyu Zhang, Eitan Friedman, Heiko Becher, János Papp, Thomas Rüdiger, Alison M. Dunning, Daniele Campa, Alfons Meindl, Lothar Häberle, Ana Blanco, Eric Hahnen, Barbara Wappenschmidt, Elaine F. Harkness, Audrey Y. Jung, Guanghao Qi, Zumuruda Abu Ful, Maria A. Caligo, Priyanka Sharma, Håkan Olsson, Elke M van Veen, Marion Piedmonte, Linetta B. Koppert, Usha Menon, Laura Matricardi, Jonine D. Figueroa, Wei Zheng, Milena Jakimovska, Katarzyna Białkowska, Renske Keeman, Matti A. Rookus, William J. Tapper, J. Peto, Paul L. Auer, Andreas Schneeweiss, Xiao-Ou Shu, Miriam Dwek, Elvira Mingazheva, Hermann Brenner, Emilija Lazarova, Atocha Romero, Rulla M. Tamimi, Laura Papi, Hans Wildiers, Catriona McLean, Montserrat Garcia-Closas, Matthias Rübner, Thomas Brüning, Graham G. Giles, Robert J. MacInnis, Hans Christiansen, Sten Cornelissen, Paul A. James, Georgia Chenevix-Trench, Tjoung-Won Park-Simon, Nilanjan Chatterjee, D. Gareth Evans, Ignacio Briceño, Mary B. Daly, Annegien Broeks, Evgeny N. Imyanitov, Jonathan Beesley, Snezhana Smichkoska, Thilo Dörk, Yon-Dschun Ko, Paolo Peterlongo, Celine M. Vachon, Claire Mulot, Kristiina Aittomäki, Liene Nikitina-Zake, Manuel R. Teixeira, Edith Olah, Florentia Fostira, Beth N. Peshkin, Pierre Laurent-Puig, M. B. Terry, Michael T. Parsons, Anna González-Neira, Julie Lecarpentier, Jacek Gronwald, Fergus J. Couch, Mariarosaria Calvello, Leigha Senter, Ute Hamann, Brigitte Rack, Marco Montagna, Simon A. Gayther, Barbara Burwinkel, Anne-Vibeke Lænkholm, Irene L. Andrulis, Sabine Behrens, Beth Y. Karlan, Anthony J. Swerdlow, Marjanka K. Schmidt, Cari M. Kitahara, Emmanouil Saloustros, Dijana Plaseska-Karanfilska, Melissa A. Troester, Diana Torres, Daniel Barrowdale, Elinor J. Sawyer, Hiltrud Brauch, Minouk J. Schoemaker, Dale P. Sandler, José A. García-Sáenz, Jennifer Stone, Qin Wang, Conxi Lázaro, Paolo Radice, Jan Lubinski, Jose E. Castelao, Natalia Bogdanova, Drakoulis Yannoukakos, Davide Bondavalli, Kristan J. Aronson, Gad Rennert, Wing-Yee Lo, Robert N. Hoover, Dominique Stoppa-Lyonnet, Nadine Tung, Stephen J. Chanock, Andrew K. Godwin, Angela Cox, Maartje J. Hooning, Anthony Howell, Volker Arndt, Penny Soucy, Jenny Chang-Claude, Kathleen Claes, Olufunmilayo I. Olopade, Jeffrey N. Weitzel, Stig E. Bojesen, Sara Y Brucker, Darcy L. Thull, Darya Prokofyeva, Taru A. Muranen, Ben Schöttker, Orland Diez, Susan M. Gapstur, Sarah Sampson, Bernardo Bonanni, Per Hall, Ana Vega, Medical Oncology, Surgery, and Clinical Genetics
Subjects: Oncology, medicine.medical_specialty, Linkage disequilibrium, Carcinogenesis, Estrogen receptor, Genome-wide association study, Breast Neoplasms, Triple Negative Breast Neoplasms, Biology, Gene mutation, Linkage Disequilibrium, Càncer de mama, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, Genetics, Genetic predisposition, medicine, Humans, Genetic Predisposition to Disease, Carcinogènesi, Triple-negative breast cancer, 030304 developmental biology, Medicinsk genetik, 0303 health sciences, Genetic heterogeneity, BRCA1 Protein, medicine.disease, 3. Good health, Case-Control Studies, Female, Mutation, Genome-Wide Association Study, Medical Genetics, 030217 neurology & neurosurgery
Abstract: Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype(1-3). 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 < 5.0 x 10(-8)), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.
Published: 2020
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36. Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

Author: Elinor Sawyer, Rebecca Roylance, Christos Petridis, Mark N Brook, Salpie Nowinski, Efterpi Papouli, Olivia Fletcher, Sarah Pinder, Andrew Hanby, Kelly Kohut, Patricia Gorman, Michele Caneppele, Julian Peto, Isabel Dos Santos Silva, Nichola Johnson, Ruth Swann, Miriam Dwek, Katherine-Anne Perkins, Cheryl Gillett, Richard Houlston, Gillian Ross, Paolo De Ieso, Melissa C Southey, John L Hopper, Elena Provenzano, Carmel Apicella, Jelle Wesseling, Sten Cornelissen, Renske Keeman, Peter A Fasching, Sebastian M Jud, Arif B Ekici, Matthias W Beckmann, Michael J Kerin, Federick Marme, Andreas Schneeweiss, Christof Sohn, Barbara Burwinkel, Pascal Guénel, Therese Truong, Pierre Laurent-Puig, Pierre Kerbrat, Stig E Bojesen, Børge G Nordestgaard, Sune F Nielsen, Henrik Flyger, Roger L Milne, Jose Ignacio Arias Perez, Primitiva Menéndez, Javier Benitez, Hermann Brenner, Aida Karina Dieffenbach, Volker Arndt, Christa Stegmaier, Alfons Meindl, Peter Lichtner, Rita K Schmutzler, Magdalena Lochmann, Hiltrud Brauch, Hans-Peter Fischer, Yon-Dschun Ko, GENICA Network, Heli Nevanlinna, Taru A Muranen, Kristiina Aittomäki, Carl Blomqvist, Natalia V Bogdanova, Thilo Dörk, Annika Lindblom, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, Georgia Chenevix-Trench, KConFab Investigators, Diether Lambrechts, Caroline Weltens, Erik Van Limbergen, Sigrid Hatse, Jenny Chang-Claude, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Paolo Radice, Paolo Peterlongo, Bernardo Bonanni, Sara Volorio, Graham G Giles, Gianluca Severi, Laura Baglietto, Catriona A McLean, Christopher A Haiman, Brian E Henderson, Fredrick Schumacher, Loic Le Marchand, Jacques Simard, Mark S Goldberg, France Labrèche, Martine Dumont, Vessela Kristensen, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Saila Kauppila, Irene L Andrulis, Julia A Knight, Gord Glendon, Anna Marie Mulligan, Peter Devillee, Rob A E M Tollenaar, Caroline M Seynaeve, Mieke Kriege, Jonine Figueroa, Stephen J Chanock, Mark E Sherman, Maartje J Hooning, Antoinette Hollestelle, Ans M W van den Ouweland, Carolien H M van Deurzen, Jingmei Li, Kamila Czene, Keith Humphreys, Angela Cox, Simon S Cross, Malcolm W R Reed, Mitul Shah, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Anthony Swerdlow, Alan Ashworth, Nicholas Orr, Minouk Schoemaker, Fergus J Couch, Emily Hallberg, Anna González-Neira, Guillermo Pita, M Rosario Alonso, Daniel C Tessier, Daniel Vincent, Francois Bacot, Manjeet K Bolla, Qin Wang, Joe Dennis, Kyriaki Michailidou, Alison M Dunning, Per Hall, Doug Easton, Paul Pharoah, Marjanka K Schmidt, Ian Tomlinson, and Montserrat Garcia-Closas
Subjects: Genetics, QH426-470
Abstract: Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P
Published: 2014
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37. Breast cancer risks associated with missense variants in breast cancer susceptibility genes

Author: Douglas F. Easton, Manuela Gago-Dominguez, Marina Bermisheva, Marike Gabrielson, Michael J. Madsen, Antoinette Hollestelle, Joe Dennis, Roger L. Milne, Per Hall, Andreas Hadjisavvas, Muriel A. Adank, Melissa C. Southey, Anthony Howell, Qin Wang, Thilo Dörk, Elza Khusnutdinova, Nicola J. Camp, Miguel de la Hoya, Pascal Guénel, Archie Campbell, Gord Glendon, Javier Benitez, Sgbcc Investigators, Manjeet K. Bolla, Jonine D. Figueroa, Paolo Radice, Maaike P.G. Vreeswijk, William G. Newman, Soo Hwang Teo, Anna Jakubowska, Paul D.P. Pharoah, Sara Margolin, Thomas U. Ahearn, Mitul Shah, Eric Hahnen, Matthias W. Beckmann, Dimitrios Mavroudis, Elinor J. Sawyer, Paolo Peterlongo, Artitaya Lophatananon, Melanie Gündert, Maria A. Loizidou, Xueling Sim, Irene L. Andrulis, Ignacio Briceño, Mehdi Manoochehri, Rita K. Schmutzler, Maija Suvanto, Sara Carvalho, Amanda B. Spurdle, Georgia Chenevix-Trench, Marjanka K. Schmidt, Graham G. Giles, Peter A. Fasching, Inge M. M. Lakeman, Vessela N. Kristensen, Leila Dorling, Annika Lindblom, Harald Surowy, Jan C. Oosterwijk, Diana Torres, Nur Aishah Taib, Xiaohong R. Yang, D. Gareth Evans, Päivi Auvinen, Heli Nevanlinna, Sabine Behrens, Arto Mannermaa, Christi J. van Asperen, Anna González-Neira, Ian Tomlinson, Thérèse Truong, Heiko Becher, J. Margriet Collée, Jenny Chang-Claude, Mikael Hartman, Michael T. Parsons, Jamie Allen, Henrik Flyger, Sue K. Park, Craig Luccarini, Sung-Won Kim, Stephan M. Heijl, Montserrat Garcia-Closas, Cristina Fortuno, Jingmei Li, Peter Devilee, Yon-Dschun Ko, Reiner Hoppe, Stig E. Bojesen, Regina Waltes, Frans B. L. Hogervorst, Alison M. Dunning, Kenneth Muir, Mikael Eriksson, Bas Vroling, Jan Lubinski, Jose E. Castelao, Stephen J. Chanock, Natalia Bogdanova, Anders Kvist, Michael Bremer, Emmanouil Saloustros, Kamila Czene, kConFab Investigators, Elaine F. Harkness, Audrey Y. Jung, and Ute Hamann
Subjects: Genetics, 0303 health sciences, PALB2, Biology, medicine.disease, Logistic regression, Lower risk, Breast cancer susceptibility genes, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, 030220 oncology & carcinogenesis, medicine, Missense mutation, CHEK2, Gene, 030304 developmental biology
Abstract: BACKGROUNDProtein truncating variants in ATM, BRCA1, BRCA2, CHEK2 and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain.METHODSCombining 59,639 breast cancer cases and 53,165 controls, we sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1,146 training variants), BRCA1 (644), BRCA2 (1,425), CHEK2 (325) and PALB2 (472). We evaluated breast cancer risks according to five in-silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated.RESULTSThe most predictive in-silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1 and BRCA2, data were compatible with small subsets (approximately 7%, 2% and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47-2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best fitting models were well calibrated in the validation set.CONCLUSIONSThese results will inform risk prediction models and the selection of candidate variants for functional assays, and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility.
Published: 2021
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38. The Surgical Management of Brain Metastases in Non-Small Cell Lung Cancer (NSCLC): Identification of the Early Laboratory and Clinical Determinants of Survival

Author: Katjana S Schwab, Christina Schaub, Muriel Heimann, Lars Eichhorn, Jennifer Landsberg, Johannes Weller, Erdem Güresir, Christian Bode, Niklas Schäfer, Felix Lehmann, Hartmut Vatter, Alexander Radbruch, Frank A. Giordano, Yon-Dschun Ko, Matthias Schneider, Ulrich Herrlinger, and Patrick Schuss
Subjects: Mechanical ventilation, Oncology, medicine.medical_specialty, Multivariate analysis, business.industry, medicine.medical_treatment, overall survival, Cancer, non-small cell lung cancer (NSCLC), General Medicine, Disease, Perioperative, medicine.disease, surgical management, Article, lung cancer, Internal medicine, brain metastases, medicine, Medicine, Lung cancer, business, Adverse effect
Abstract: Background: Brain metastases (BM) indicate advanced states of cancer disease and cranial surgery represents a common treatment modality. In the present study, we aimed to identify the risk factors for a reduced survival in patients receiving a surgical treatment of BM derived from non-small cell lung cancer (NSCLC). Methods: A total of 154 patients with NSCLC that had been surgically treated for BM at the authors’ institution between 2013 and 2018 were included for a further analysis. A multivariate analysis was performed to identify the predictors of a poor overall survival (OS). Results: The median overall survival (mOS) was 11 months (95% CI 8.2–13.8). An age &gt, 65 years, the infratentorial location of BM, elevated preoperative C-reactive protein levels, a perioperative red blood cell transfusion, postoperative prolonged mechanical ventilation (&gt, 48 h) and the occurrence of postoperative adverse events were identified as independent factors of a poor OS. Conclusions: The present study identified several predictors for a worsened OS in patients that underwent surgery for BM of NSCLC. These findings might guide a better risk/benefit assessment in the course of metastatic NSCLC therapy and might help to more sufficiently cope with the challenges of cancer therapy in these advanced stages of disease.
Published: 2021

39. Combined Assessment of Preoperative Frailty and Sarcopenia Allows the Prediction of Overall Survival in Patients with Lung Cancer (NSCLC) and Surgically Treated Brain Metastasis

Author: Christian Bode, Inja Ilic, Frank A. Giordano, Ulrich Herrlinger, Niklas Schäfer, Felix Lehmann, Erdem Güresir, Matthias Schneider, Lars Eichhorn, Muriel Heimann, Valeri Borger, Andreas H. Jacobs, Jennifer Landsberg, Anton Faron, Yon-Dschun Ko, Patrick Schuss, Alexander Radbruch, Anna-Laura Potthoff, and Hartmut Vatter
Subjects: Oncology, Cancer Research, medicine.medical_specialty, overall survival, frailty, Article, Resection, sarcopenia, 03 medical and health sciences, 0302 clinical medicine, Age groups, brain metastases, Internal medicine, medicine, Overall survival, non-small cell lung cancer, outcome, In patient, Lung cancer, RC254-282, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 030220 oncology & carcinogenesis, Sarcopenia, Non small cell, business, human activities, 030217 neurology & neurosurgery, Brain metastasis
Abstract: Simple Summary Patients with brain metastasis are at a severe stage of cancer, and brain surgery can prevent neurological morbidity. However, the success of brain surgery might require a patient’s physical integrity prior to the operation. In the present study, we asked whether a preoperative physical decline affects survival in patients with brain metastasis from lung cancer. In order to measure the physical condition, we used a commonly-known index—the so-called frailty index—and additionally measured the thickness of a particular masticatory muscle as muscle loss correlates to physical decline. We found that a decreased muscle thickness was accompanied by worsened survival for patients < 65 years and an increased frailty index correlated to worsened survival for patients ≥ 65 years. These results encourage to use of the frailty index and muscle thickness as easily available parameters in order to more sufficiently estimate individual treatment success in patients with metastatic lung cancer. Abstract Neurosurgical resection represents an important therapeutic pillar in patients with brain metastasis (BM). Such extended treatment modalities require preoperative assessment of patients’ physical status to estimate individual treatment success. The aim of the present study was to analyze the predictive value of frailty and sarcopenia as assessment tools for physiological integrity in patients with non-small cell lung cancer (NSCLC) who had undergone surgery for BM. Between 2013 and 2018, 141 patients were surgically treated for BM from NSCLC at the authors’ institution. The preoperative physical condition was assessed by the temporal muscle thickness (TMT) as a surrogate parameter for sarcopenia and the modified frailty index (mFI). For the ≥65 aged group, median overall survival (mOS) significantly differed between patients classified as ‘frail’ (mFI ≥ 0.27) and ‘least and moderately frail’ (mFI < 0.27) (15 months versus 11 months (p = 0.02)). Sarcopenia revealed significant differences in mOS for the
Published: 2021
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40. Rare Copy Number Variants (CNVs) and Breast Cancer Risk

Author: Vessela N. Kristensen, Abctb Investigators, Elinor J. Sawyer, Jose Esteban Castelao, Christine L. Clarke, Argyrios Ziogas, Natalia Bogdanova, Pascal Guénel, Lin Fritschi, Marina Bermisheva, Alicja Wolk, Anthony J. Swerdlow, Graham G. Giles, Antoinette Hollestelle, Camilla Wendt, Stig E. Bojesen, Reiner Hoppe, Laure Dossus, Marike Gabrielson, Doug Easton, Dimitrios Mavroudis, Rulla M. Tamimi, Manuela Gago-Dominguez, Roger L. Milne, Kristan J. Aronson, Kyriaki Michailidou, Logan C. Walker, Siranoush Manoukian, Taru A. Muranen, Melissa A. Troester, Celine M. Vachon, Javier Benítez, Alicja Lukomska, Martha S. Linet, Heli Nevanlinna, Marjanka K. Schmidt, Thilo Dörk, Kubelka-Sabit K, Rita K. Schmutzler, Antonenkova Nn, Pharoah Pd, Anna González-Neira, H Brenner, Dijana Plaseska-Karanfilska, Fergus J. Couch, Ian Tomlinson, Thérèse Truong, Sabine Behrens, A. H. Eliassen, Peter A. Fasching, Cox A, P. Kraft, Wei Zheng, Rudolph Kaaks, Tyrer Jp, Renske Keeman, Rachel A. Murphy, Georgia Chenevix-Trench, Dale P. Sandler, Olivia Fletcher, Leila Dorling, Sara Margolin, Thomas U. Ahearn, Agnes Jager, Christopher A. Haiman, Lauren R. Teras, Tjoung-Won Park-Simon, James V. Lacey, Per Hall, Matthias W. Beckmann, Jacques Simard, Michael Jones, Collee Jm, D G Evans, Shibli R, Investigators k, Katri Pylkäs, Xiaohong R. Yang, Esther M. John, Eric Hahnen, D Lambrechts, Peter Devilee, Kamila Czene, Jonine D. Figueroa, Alison M. Dunning, Hoda Anton-Culver, Stella Koutros, Melissa C. Southey, Kosma, Joe Dennis, Yon-Dschun Ko, Mary Beth Terry, Jenny Chang-Claude, Anthony Howell, Beane Freeman Le, Charles M. Perou, Qinghua Wang, Henrik Flyger, Nichola Johnson, John L. Hopper, Paolo Peterlongo, Simon S. Cross, Jack A. Taylor, Audrey Y. Jung, Robert Winqvist, Håkan Olsson, Arndt, Irene L. Andrulis, Nicole L. Larson, Penny Soucy, Anna Jakubowska, Cari M. Kitahara, Janet E. Olson, Emmanouil Saloustros, Elza Khusnutdinova, Manjeet K. Bolla, M Garcia-Closas, Ann Smeets, Mikael Eriksson, Allison W. Kurian, Gadi Rennert, and Arto Mannermaa
Subjects: Genetics, 0303 health sciences, Cancer, Disease, Biology, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, 030220 oncology & carcinogenesis, Gene duplication, medicine, Human genome, Copy-number variation, Gene, CHEK2, 030304 developmental biology
Abstract: BackgroundCopy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data.ResultsGene burden tests detected the strongest association for deletions in BRCA1 (P= 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P= 0.0008), ATM (P= 0.002) and BRCA2 (P= 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci.ConclusionsThis is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.
Published: 2021
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41. MicroRNA related polymorphisms and breast cancer risk.

Author: Sofia Khan, Dario Greco, Kyriaki Michailidou, Roger L Milne, Taru A Muranen, Tuomas Heikkinen, Kirsimari Aaltonen, Joe Dennis, Manjeet K Bolla, Jianjun Liu, Per Hall, Astrid Irwanto, Keith Humphreys, Jingmei Li, Kamila Czene, Jenny Chang-Claude, Rebecca Hein, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Olivia Fletcher, Julian Peto, Isabel dos Santos Silva, Nichola Johnson, Lorna Gibson, Zoe Aitken, John L Hopper, Helen Tsimiklis, Minh Bui, Enes Makalic, Daniel F Schmidt, Melissa C Southey, Carmel Apicella, Jennifer Stone, Quinten Waisfisz, Hanne Meijers-Heijboer, Muriel A Adank, Rob B van der Luijt, Alfons Meindl, Rita K Schmutzler, Bertram Müller-Myhsok, Peter Lichtner, Clare Turnbull, Nazneen Rahman, Stephen J Chanock, David J Hunter, Angela Cox, Simon S Cross, Malcolm W R Reed, Marjanka K Schmidt, Annegien Broeks, Laura J Van't Veer, Frans B Hogervorst, Peter A Fasching, Michael G Schrauder, Arif B Ekici, Matthias W Beckmann, Stig E Bojesen, Børge G Nordestgaard, Sune F Nielsen, Henrik Flyger, Javier Benitez, Pilar M Zamora, Jose I A Perez, Christopher A Haiman, Brian E Henderson, Fredrick Schumacher, Loic Le Marchand, Paul D P Pharoah, Alison M Dunning, Mitul Shah, Robert Luben, Judith Brown, Fergus J Couch, Xianshu Wang, Celine Vachon, Janet E Olson, Diether Lambrechts, Matthieu Moisse, Robert Paridaens, Marie-Rose Christiaens, Pascal Guénel, Thérèse Truong, Pierre Laurent-Puig, Claire Mulot, Frederick Marme, Barbara Burwinkel, Andreas Schneeweiss, Christof Sohn, Elinor J Sawyer, Ian Tomlinson, Michael J Kerin, Nicola Miller, Irene L Andrulis, Julia A Knight, Sandrine Tchatchou, Anna Marie Mulligan, Thilo Dörk, Natalia V Bogdanova, Natalia N Antonenkova, Hoda Anton-Culver, Hatef Darabi, Mikael Eriksson, Montserrat Garcia-Closas, Jonine Figueroa, Jolanta Lissowska, Louise Brinton, Peter Devilee, Robert A E M Tollenaar, Caroline Seynaeve, Christi J van Asperen, Vessela N Kristensen, kConFab Investigators, Australian Ovarian Cancer Study Group, Susan Slager, Amanda E Toland, Christine B Ambrosone, Drakoulis Yannoukakos, Annika Lindblom, Sara Margolin, Paolo Radice, Paolo Peterlongo, Monica Barile, Paolo Mariani, Maartje J Hooning, John W M Martens, J Margriet Collée, Agnes Jager, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Graham G Giles, Catriona McLean, Hiltrud Brauch, Thomas Brüning, Yon-Dschun Ko, GENICA Network, Hermann Brenner, Aida Karina Dieffenbach, Volker Arndt, Christa Stegmaier, Anthony Swerdlow, Alan Ashworth, Nick Orr, Michael Jones, Jacques Simard, Mark S Goldberg, France Labrèche, Martine Dumont, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, Arto Mannermaa, Ute Hamann, Georgia Chenevix-Trench, Carl Blomqvist, Kristiina Aittomäki, Douglas F Easton, and Heli Nevanlinna
Subjects: Medicine, Science
Abstract: Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.
Published: 2014
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42. Tumor-Associated Epilepsy in Patients With Brain Metastases: Necrosis-to-Tumor Ratio Forecasts Postoperative Seizure Freedom

Author: Yon-Dschun Ko, Muriel Heimann, Erdem Güresir, Niklas Schäfer, Ulrich Herrlinger, Felix Lehmann, Rainer Surges, Anna-Laura Potthoff, Majd Bahna, Lars Eichhorn, Patrick Schuss, Motaz Hamed, Christina Schaub, Christian Bode, Johannes Weller, Alexander Radbruch, Valeri Borger, Hartmut Vatter, and Matthias Schneider
Subjects: Freedom, medicine.medical_specialty, Necrosis, Neurosurgical Procedures, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Quality of life, Seizures, medicine, Humans, In patient, Retrospective Studies, business.industry, Brain Neoplasms, Cancer, General Medicine, Seizure freedom, medicine.disease, Surgery, Treatment Outcome, 030220 oncology & carcinogenesis, Concomitant, Quality of Life, Neurology (clinical), Neurosurgery, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Surgical resection is highly effective in the treatment of tumor-related epilepsy (TRE) in patients with brain metastases (BM). Nevertheless, some patients suffer from postoperative persistent epilepsy which negatively impacts health-related quality of life. Therefore, early identification of patients with potentially unfavorable seizure outcome after BM resection is important. Patients with TRE that had undergone surgery for BM at the authors’ institution between 2013 and 2018 were analyzed with regard to preoperatively identifiable risk factors for unfavorable seizure outcome. Tumor tissue and tumor necrosis ratios were assessed volumetrically. According to the classification of the International League Against Epilepsy (ILAE), seizure outcome was categorized as favorable (ILAE 1) and unfavorable (ILAE 2–6) after 3 months in order to avoid potential interference with adjuvant cancer treatment. Among all 38 patients undergoing neurosurgical treatment for BM with concomitant TRE, 34 patients achieved a favorable seizure outcome (90%). Unfavorable seizure outcome was significantly associated with larger tumor volumes (p = 0.012), a midline shift > 7 mm (p = 0.025), and a necrosis/tumor volume ratio > 0.2 (p = 0.047). The present study identifies preoperatively collectable risk factors for unfavorable seizure outcome in patients with BM and TRE. This might enable to preselect for highly vulnerable patients with postoperative persistent epilepsy who might benefit from accompanying neuro-oncological expertise during further systemical treatment regimes.
Published: 2021
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43. Prognostic Value of Preoperative Inflammatory Markers in Melanoma Patients with Brain Metastases

Author: Katjana S Schwab, Johannes Weller, Niklas Schäfer, Hartmut Vatter, Patrick Schuss, Felix Lehmann, Anna-Laura Potthoff, Alexander Radbruch, Christian Bode, Lars Eichhorn, Frank A. Giordano, Jennifer Landsberg, Ulrich Herrlinger, Christina Schaub, Valeri Borger, Erdem Güresir, Matthias Schneider, Yon-Dschun Ko, and Muriel Heimann
Subjects: medicine.medical_specialty, overall survival, lcsh:Medicine, Inflammation, Disease, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, melanoma, brain metastasis, 030304 developmental biology, 0303 health sciences, Receiver operating characteristic, business.industry, Melanoma, lcsh:R, surgical resection, General Medicine, medicine.disease, Confidence interval, Peripheral, inflammation, 030220 oncology & carcinogenesis, Cohort, medicine.symptom, business, Brain metastasis
Abstract: Background: Metastatic melanoma disease is accompanied by highly systemic inflammatory responses. The prognostic value of preoperative laboratory inflammation markers in brain metastatic melanoma patients has not been adequately investigated so far. Methods: Preoperative inflammatory blood parameters were correlated to overall survival (OS) rates in melanoma patients that underwent surgery for brain metastasis (BM) between 2013 and 2019 at the authors’ institution. Receiver operating characteristic (ROC) analyses were used for cutoff determination of routine laboratory parameters. Results: Median OS in the present cohort of 30 melanoma patients with surgically treated BM was 7 months (95% confidence interval (CI) 5.7–8.3). Initial elevated C-reactive protein (CRP) levels (&gt, 10 mg/L), neutrophil-to-lymphocyte ratio (NLR) ≥ 4, platelet-to-lymphocyte ratio (PLR) ≥ 145, and lymphocyte-to-monocyte ratio (LMR) &lt, 2 were associated with significantly reduced OS rates. Conclusions: The present study identifies several preoperative peripheral inflammatory markers as indicators for poor prognosis in melanoma patients with BM undergoing neurosurgical treatment. Elevated initial CRP values, higher NLR and PLR, and lower LMR were associated with reduced OS and, thus, might be incorporated into preoperative interdisciplinary treatment planning and counseling for affected patients.
Published: 2021
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44. Depth of Response to Isatuximab, Carfilzomib, Lenalidomide and Dexamethasone (Isa-KRd) in Front-Line Treatment of High-Risk Multiple Myeloma: Interim Analysis of the GMMG-CONCEPT Trial

Author: Lisa B. Leypoldt, Anne Marie Asemissen, Britta Besemer, Mathias Haenel, Igor Wolfgang Blau, Martin Görner, Yon-Dschun Ko, Hans Christian Reinhardt, Peter Staib, Christoph Mann, Raphael Lutz, Markus Munder, Ullrich Graeven, Rudolf Peceny, Hans Salwender, Anna Jauch, Manola Zago, Axel Benner, Diana Tichy, Carsten Bokemeyer, Hartmut Goldschmidt, Katja C. Weisel, and German Speaking Myeloma Multicenter Group (GMMG)
Subjects: medicine.medical_specialty, education.field_of_study, Study drug, Population, Ethics committee, Front line, Interim analysis, Safety profile, Informed consent, Family medicine, Induction therapy, medicine, Business, education
Abstract: Background: High-risk (HR) multiple myeloma (MM) has an impaired prognostic outcome. Addition of anti-CD38 monoclonal antibodies to standard-of-care regimens improved response rates and depth of response. Here, we report a prespecified interim analysis (IA) following induction therapy with the quadruplet regimen isatuximab, carfilzomib, lenalidomide and dexamethasone (Isa-KRd) in newly diagnosed (ND) HR MM patients (pts) in the phase II multicentric GMMG-CONCEPT trial (NCT03104842). Methods: 153 pts with HR NDMM were enrolled into the trial, the IA reports on the first 50 pts evaluable for IA. Pts receive Isa-KRd in induction, consolidation and Isa-KR maintenance. Transplant eligible pts undergo high-dose therapy. This IA reports on overall response rates (ORR) during induction. Findings: 50 pts were included in the IA population for ORR. HR MM was defined by del17p in 52%, t(4;14) in 38%, t(14;16) in 12% and > 3 copies 1q21 in 42% and ISS stage 2/3 disease. 46/50 pts completed induction treatment. ORR was 100%, with 5 pts (10·0%) showing partial response (PR), 22 (44·0%; including 4 in arm B) very good partial response (VGPR) and 23 (46·0%) complete response (CR). Hematologic grade 3/4 treatment-emergent adverse events (≥ 10%) were neutropenia (34·0%), leukopenia (26·0%) and thrombocytopenia (14·0%). Main non-hematologic toxicities grade 3/4 were hypertension (12·0%) and infection (8·0%). Interpretation: We report for the first time on a trial investigating Isa-KRd quadruplet treatment in solely HR NDMM. Isa-KRd induction induces rapid and deep responses. The overall safety profile is consistent with previous reports. Trial Registration: The trial is registered at clinicaltrials.gov (NCT03104842). Funding Statement: Study drug and financial support by Amgen, Celgene-BMS and Sanofi. Declaration of Interests: Dr. Leypoldt reports grants and non-financial support from Celgene-BMS, grants and non-financial support from Sanofi, grants and non-financial support from Amgen, during the conduct of the study; non-financial support from GSK, non-financial support from Abbvie, outside the submitted work; Dr. Asemissen has nothing to disclose. Dr. Besemer has nothing to disclose. Dr. Hanel reports personal fees from Celgene, personal fees from Novartis, personal fees from Takeda, personal fees from Amgen, during the conduct of the study; Dr. Blau has nothing to disclose. Dr. Gorner has nothing to disclose. Dr. Ko has nothing to disclose. Dr. Reinhardt reports personal fees from Abbvie, grants from Gilead, personal fees from Merck, other from CDL Therapeutics GmbH, outside the submitted work; Dr. Staib reports grants, personal fees, non-financial support and other from Abbvie, grants, personal fees, non-financial support and other from Amgen, grants, personal fees, non-financial support and other from Celgene, grants, personal fees, non-financial support and other from Janssen-Cilag, grants, personal fees, non-financial support and other from Novartis, grants, personal fees, non-financial support and other from Gilead, grants, personal fees, non-financial support and other from Pfizer, grants, personal fees, non-financial support and other from Roche, outside the submitted work; Dr. Mann has nothing to disclose. Dr. Lutz has nothing to disclose. Dr. Munder reports personal fees and non-financial support from Janssen, personal fees and non-financial support from Amgen, grants from Incyte, personal fees and non-financial support from BMS, personal fees from Abbvie, personal fees from Sanofi, personal fees from GSK, personal fees from Takeda, outside the submitted work; Dr. Graeven reports personal fees from Amgen, personal fees and non-financial support from Boehringer Ingelheim, personal fees from Daichi Sankyo, personal fees from Servier, personal fees from Celgene, personal fees from Astra Zeneca, personal fees from Johnson Johnson, non-financial support from Merck, personal fees from MSD, personal fees from BMS, during the conduct of the study; Dr. Peceny reports grants and personal fees from Sanofi Genzyme, grants from Novartis, grants from DRK Blutspendedienst NSTOB, grants from Boehringer Ingelheim Pharma GmbH & Co KG, grants from Celgene, outside the submitted work; Dr. Salwender reports personal fees from Bristol-Myers Squibb/Celgene, personal fees from Janssen Cilag, personal fees from Glaxo Smith Kline, personal fees from Oncopeptides, personal fees from Takeda, personal fees from Sanofi, personal fees from AbbVie, personal fees from Amgen, outside the submitted work; Dr. Jauch has nothing to disclose. Dr. Zago has nothing to disclose. Axel Benner has nothing to disclose. Dr. Tichy has nothing to disclose. Dr. Bokemeyer reports personal fees from Sanofi Aventis, personal fees from Merck KgA, personal fees from Bristol-Myers Squibb, personal fees from Merck Sharp & Dohme, personal fees from Lilly Imclone, personal fees from Bayer Healthcare, personal fees from GSO Contract research, personal fees from AOK-Rheinland-Hamburg, personal fees from Novartis, outside the submitted work; Dr. Goldschmidt reports grants, personal fees, non-financial support and other from Amgen, grants, personal fees, non-financial support and other from BMS, grants, personal fees, non-financial support and other from Celgene, grants, personal fees, and other from Chugai, grants, personal fees, non-financial support and other from Janssen, grants, personal fees, non-financial support and other from Sanofi, other from Incyte, other from Molecular Partners, other from Merck Sharp and Dohme (MSD), other from Mundipharma, grants, personal fees, non-financial support and other from Takeda, personal fees and other from Novartis, personal fees from Adaptive Biotechnology, personal fees from GlaxoSmithKline (GSK), outside the submitted work. Dr. Weisel reports grants from AMGEN, grants from Celgene, grants from Sanofi, during the conduct of the study; grants, personal fees and non-financial support from Amgen, personal fees and non-financial support from BMS, grants, personal fees and non-financial support from Celgene, personal fees from Adaptive Biotech, grants, personal fees and non-financial support from Janssen, personal fees and non-financial support from GSK, personal fees from Karyopharm, grants, personal fees and non-financial support from Sanofi, personal fees and non-financial support from Takeda, personal fees from Oncopeptides, personal fees from Roche, outside the submitted work. Ethics Approval Statement: All patients provided written informed consent. The trial was approved by the competent authorities and the Tuebingen University Ethics Committee.
Published: 2021
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45. Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk

Author: Iris Kramer, Maartje J. Hooning, Nasim Mavaddat, Michael Hauptmann, Renske Keeman, Ewout W. Steyerberg, Daniele Giardiello, Antonis C. Antoniou, Paul D.P. Pharoah, Sander Canisius, Zumuruda Abu-Ful, Irene L. Andrulis, Hoda Anton-Culver, Kristan J. Aronson, Annelie Augustinsson, Heiko Becher, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Bernardo Bonanni, Hiltrud Brauch, Michael Bremer, Sara Y. Brucker, Barbara Burwinkel, Jose E. Castelao, Tsun L. Chan, Jenny Chang-Claude, Stephen J. Chanock, Georgia Chenevix-Trench, Ji-Yeob Choi, Christine L. Clarke, J. Margriet Collée, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Peter Devilee, Thilo Dörk, Isabel dos-Santos-Silva, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, D. Gareth Evans, Peter A. Fasching, Henrik Flyger, Manuela Gago-Dominguez, Montserrat García-Closas, José A. García-Sáenz, Graham G. Giles, David E. Goldgar, Anna González-Neira, Christopher A. Haiman, Niclas Håkansson, Ute Hamann, Mikael Hartman, Bernadette A.M. Heemskerk-Gerritsen, Antoinette Hollestelle, John L. Hopper, Ming-Feng Hou, Anthony Howell, Hidemi Ito, Milena Jakimovska, Anna Jakubowska, Wolfgang Janni, Esther M. John, Audrey Jung, Daehee Kang, C. Marleen Kets, Elza Khusnutdinova, Yon-Dschun Ko, Vessela N. Kristensen, Allison W. Kurian, Ava Kwong, Diether Lambrechts, Loic Le Marchand, Jingmei Li, Annika Lindblom, Jan Lubiński, Arto Mannermaa, Mehdi Manoochehri, Sara Margolin, Keitaro Matsuo, Dimitrios Mavroudis, Alfons Meindl, Roger L. Milne, Anna Marie Mulligan, Taru A. Muranen, Susan L. Neuhausen, Heli Nevanlinna, William G. Newman, Andrew F. Olshan, Janet E. Olson, Håkan Olsson, Tjoung-Won Park-Simon, Julian Peto, Christos Petridis, Dijana Plaseska-Karanfilska, Nadege Presneau, Katri Pylkäs, Paolo Radice, Gad Rennert, Atocha Romero, Rebecca Roylance, Emmanouil Saloustros, Elinor J. Sawyer, Rita K. Schmutzler, Lukas Schwentner, Christopher Scott, Mee-Hoong See, Mitul Shah, Chen-Yang Shen, Xiao-Ou Shu, Sabine Siesling, Susan Slager, Christof Sohn, Melissa C. Southey, John J. Spinelli, Jennifer Stone, William J. Tapper, Maria Tengström, Soo Hwang Teo, Mary Beth Terry, Rob A.E.M. Tollenaar, Ian Tomlinson, Melissa A. Troester, Celine M. Vachon, Chantal van Ongeval, Elke M. van Veen, Robert Winqvist, Alicja Wolk, Wei Zheng, Argyrios Ziogas, Douglas F. Easton, Per Hall, Marjanka K. Schmidt, Anne-Lise Børresen-Dale, Kristine Sahlberg, Lars Ottestad, Rolf Kåresen, Ellen Schlichting, Marit Muri Holmen, Toril Sauer, Vilde Haakensen, Olav Engebråten, Bjørn Naume, Alexander Fosså, Cecile Kiserud, Kristin Reinertsen, Åslaug Helland, Margit Riis, Jürgen Geisler, Grethe Grenaker Alnæs, Christine Clarke, Deborah Marsh, Rodney Scott, Robert Baxter, Desmond Yip, Jane Carpenter, Alison Davis, Nirmala Pathmanathan, Peter Simpson, J. Dinny Graham, Mythily Sachchithananthan, David Amor, Lesley Andrews, Yoland Antill, Rosemary Balleine, Jonathan Beesley, Ian Bennett, Michael Bogwitz, Leon Botes, Meagan Brennan, Melissa Brown, Michael Buckley, Jo Burke, Phyllis Butow, Liz Caldon, Ian Campbell, Deepa Chauhan, Manisha Chauhan, Alice Christian, Paul Cohen, Alison Colley, Ashley Crook, James Cui, Margaret Cummings, Sarah-Jane Dawson, Anna deFazio, Martin Delatycki, Rebecca Dickson, Joanne Dixon, Ted Edkins, Stacey Edwards, Gelareh Farshid, Andrew Fellows, Georgina Fenton, Michael Field, James Flanagan, Peter Fong, Laura Forrest, Stephen Fox, Juliet French, Michael Friedlander, Clara Gaff, Mike Gattas, Peter George, Sian Greening, Marion Harris, Stewart Hart, Nick Hayward, John Hopper, Cass Hoskins, Clare Hunt, Paul James, Mark Jenkins, Alexa Kidd, Judy Kirk, Jessica Koehler, James Kollias, Sunil Lakhani, Mitchell Lawrence, Geoff Lindeman, Lara Lipton, Liz Lobb, Graham Mann, Sue Anne McLachlan, Bettina Meiser, Roger Milne, Sophie Nightingale, Shona O'Connell, Sarah O'Sullivan, David Gallego Ortega, Nick Pachter, Briony Patterson, Amy Pearn, Kelly Phillips, Ellen Pieper, Edwina Rickard, Bridget Robinson, Mona Saleh, Elizabeth Salisbury, Christobel Saunders, Jodi Saunus, Clare Scott, Adrienne Sexton, Andrew Shelling, Melissa Southey, Amanda Spurdle, Jessica Taylor, Renea Taylor, Heather Thorne, Alison Trainer, Kathy Tucker, Jane Visvader, Logan Walker, Rachael Williams, Ingrid Winship, Mary Ann Young, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, University of Helsinki, Medical Oncology, Public Health, Clinical Genetics, TechMed Centre, and Health Technology & Services Research
Subjects: 0301 basic medicine, Oncology, Multifactorial Inheritance, PROGNOSIS, Receptor, ErbB-2, LOCI, Gene Expression, Medical and Health Sciences, Cohort Studies, 0302 clinical medicine, ErbB-2, Neoplasms, Receptors, Genetics (clinical), Progesterone, Cancer, Genetics & Heredity, Genome, Manchester Cancer Research Centre, Confounding, Hazard ratio, 1184 Genetics, developmental biology, physiology, Neoplasms, Second Primary, Biological Sciences, Middle Aged, Prognosis, Primary tumor, Neoadjuvant Therapy, 3. Good health, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Second Primary, 030220 oncology & carcinogenesis, contralateral breast cancer, kConFab Investigators, epidemiology, Female, Risk assessment, Receptors, Progesterone, Life Sciences & Biomedicine, Cohort study, Receptor, Human, Adult, medicine.medical_specialty, ABCTB Investigators, Breast Neoplasms, Risk Assessment, White People, Article, NBCS Collaborators, 03 medical and health sciences, Breast cancer, AGE, SDG 3 - Good Health and Well-being, Asian People, Internal medicine, Breast Cancer, parasitic diseases, Genetics, medicine, Adjuvant therapy, Humans, Genetic Predisposition to Disease, Aged, Proportional Hazards Models, Science & Technology, business.industry, Proportional hazards model, Genome, Human, ResearchInstitutes_Networks_Beacons/mcrc, Prevention, 22/2 OA procedure, Estrogen Receptor alpha, medicine.disease, ASSOCIATION ANALYSIS, 030104 developmental biology, polygenic risk score, genetic, business, Genome-Wide Association Study
Abstract: Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies. ispartof: AMERICAN JOURNAL OF HUMAN GENETICS vol:107 issue:5 pages:837-848 ispartof: location:United States status: published
Published: 2020
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46. Comorbidity Burden and Presence of Multiple Intracranial Lesions Are Associated with Adverse Events after Surgical Treatment of Patients with Brain Metastases

Author: Katjana S Schwab, Ulrich Herrlinger, Lars Eichhorn, Yon-Dschun Ko, Alexander Radbruch, Christian Wispel, Hartmut Vatter, Matthias Schneider, Johannes Weller, Anna-Laura Potthoff, Niklas Schäfer, Christina Schaub, Felix Lehmann, Patrick Schuss, Leonie Weinhold, Muriel Heimann, Jennifer Landsberg, Frank A. Giordano, and Erdem Güresir
Subjects: Cancer Research, medicine.medical_specialty, Multivariate analysis, animal structures, surgical management, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, brain metastases, medicine, cancer, Adverse effect, Surgical treatment, business.industry, Cancer, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Comorbidity, Oncology, 030220 oncology & carcinogenesis, Charlson comorbidity index, Intracranial lesions, business, 030217 neurology & neurosurgery, Brain metastasis
Abstract: Surgical resection is a key treatment modality for brain metastasis (BM). However, peri- and postoperative adverse events (PAEs) might be associated with a detrimental impact on postoperative outcome. We retrospectively analyzed our institutional database with regard to patient safety indicators (PSIs), hospital-acquired conditions (HACs) and specific cranial surgery-related complications (CSCs) as high-quality metric profiles for PAEs in patients who had undergone surgery for BM in our department between 2013 and 2018. The comorbidity burden was assessed by means of the Charlson comorbidity index (CCI). A multivariate analysis was performed to identify independent predictors for the development of PAEs after surgical resection of BM. In total, 33 patients (8.5%) suffered from PAEs after surgery for BM. Of those, 17 PSI, 5 HAC and 11 CSC events were identified. Multiple brain metastases (p = 0.02) and a higher comorbidity burden (CCI &gt, 10, p = 0.003) were associated with PAEs. In-hospital mortality of patients suffering from a PAE was significantly higher than that of patients without a PAE (24% vs. 0.6%, p &lt, 0.0001). Awareness of risk factors for postoperative complications enables future prevention and optimal response, particularly in vulnerable oncological patients. The present study identified the presence of multiple brain metastases and increased comorbidity burden associated with PAEs in patients suffering from BM.
Published: 2020
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47. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial

Author: Jacobus Pfisterer, Catherine M Shannon, Klaus Baumann, Joern Rau, Philipp Harter, Florence Joly, Jalid Sehouli, Ulrich Canzler, Barbara Schmalfeldt, Andrew P Dean, Alexander Hein, Alain G Zeimet, Lars C Hanker, Thierry Petit, Frederik Marmé, Ahmed El-Balat, Rosalind Glasspool, Nikolaus de Gregorio, Sven Mahner, Tarek M Meniawy, Tjoung-Won Park-Simon, Marie-Ange Mouret-Reynier, Cristina Costan, Werner Meier, Alexander Reinthaller, Jeffrey C Goh, Tifenn L'Haridon, Sally Baron Hay, Stefan Kommoss, Andreas du Bois, Jean-Emmanuel Kurtz, Sven Ackermann, Christoph Anthuber, Mustafa Aydogdu, Angelika Baldauf, Wolfgang Bauer, Dirk Behringer, Antje Belau, Alexandra Bender, Cosima Brucker, Alexander Burges, Trygve Daabach, Dominik Denschlag, Mustafa Deryal, Steffen Dörfel, Juliane Ebert, Tanja Fehm, Susanne Maria Feidicker, Gabriele Feisel-Schwickardi, Ricardo Felberbaum, Matthias Frank, Gerhard Gebauer, Bernd Gerber, Axel Gerhardt, Andrea Grafe, Martin Griesshammer, Eva-Maria Grischke, Isolde Gröll, Martina Gropp-Meier, Dietrich Hager, Volker Hanf, Carla Verena Hannig, Peer Hantschmann, Tanja Hauzenberger, Uwe Herwig, Martin Heubner, Carsten Hielscher, Felix Hilpert, Thomas Hitschold, Manfred Hofmann, Christian Jackisch, Wolfgang Janni, Ludwig Kiesel, Yon-Dschun Ko, Hans-Joachim Koch, Petra Krabisch, Peter Krieger, Thomas Kubin, Thorsten Kühn, Björn Lampe, Peter Ledwon, Sabine Lemster, Benno Lex, Clemens Liebrich, Ralf Lorenz, Hans-Joachim Lück, Peter Mallmann, Wolfgang Meinerz, Götz Menke, Volker Möbus, Thomas Müller, Volker Müller, Tanja Neunhöffer, Angelika Ober, Gülten Oskay-Özcelik, Horst Ostertag, Martin Pölcher, Beate Rautenberg, Daniel Rein, Wilhelm Reiter, Andreas Rempen, Ingo Runnebaum, Marcus Schmidt, Sabine Schnohr, Heinz Scholz, Willibald Schröder, Eike Simon, Antje Sperfeld, Annette Steckkönig, Hans-Georg Strauß, Ronaldo Stuth, Jürgen Terhaag, Falk Thiel, Marc Thill, Oliver Tomé, Christoph Uleer, Susanne Vogel, Hermann Voß, Michael Weigel, Ulrich Winkler, Arthur Wischnik, Tobias Zeiser, Andreas Zorr, Ros Glasspool, Emma Hudson, Rachel Jones, Judith Lafleur, Christian Marth, Edgar Petru, Yoland Antill, Mary Azer, Sally Baron-Hay, Philip Beale, Stephen Begbie, Allison Black, Karen Briscoe, Andrew Dean, Jeffrey Goh, Sandra Harvey, Chee Lee, Marco Matos, Tarek Meniawy, Inger Olesen, Catherine Shannon, Paul Vasey, Sophie Abadie-Lacourtoisie, Olivier Arsene, Sophie Barthier, Célia Becuwe-Roemer, Dominique Berton-Rigaud, Maria Cappiello-Bataller, Stéphanie Catala, Francesco Del Piano, Gaël Deplanque, Raymond Despax, Nadine Dohollou, Claire Garnier-Tixidré, Julien Grenier, Emmanuel Guardiola, Anne-Claire Hardy-Bessard, Claudia Lefeuvre-Plesse, Marianne Leheurteur, Anne Lesoin, Charles-Briac Levache, Raffaele Longo, Alain Lortholary, Jérôme Meunier, Nadia Raban, Olivier Romano, Jean-Michel Vannetzel, Alain Zannetti, Cancers et préventions, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Obstetrics and Gynecology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of OB/Gyn, University Breast Center Franconia, Univeristy Hospital Erlangen, Goethe-Universität Frankfurt am Main, Mines Nantes (Mines Nantes), Division Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, Universität Heidelberg [Heidelberg] = Heidelberg University, Department of Gynecology, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hannover Medical School [Hannover] (MHH), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Medizinische Universität Wien = Medical University of Vienna, Les Hôpitaux Universitaires de Strasbourg (HUS), Department of Gynaecology, Universität Greifswald - University of Greifswald, University Hospital Düsseldorf, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, University of Rostock, Städtische Kliniken, Department of Gynecology and Obstetrics, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Hämatologie/Onkologie, Klinikum Traunstein, Department of OB/Gyn, Hospital Bayreuth, École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Department of Gynecology and Obstetrics, Center for Integrated Oncology, Bonn University Medical Center, University Hospital Bonn, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Chemical Metals Science Department, Max Planck Institute for Chemical Physics of Solids (CPfS), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Leopold Franzens Universität Innsbruck - University of Innsbruck, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre Hospitalier de Blois (CHB), CRLCC René Gauducheau, Hôpital Saint-Joseph [Marseille], Polyclinique Bordeaux Nord Aquitaine (PBNA), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), Department of Medical Oncology, CRLCC Eugène Marquis (CRLCC), Service d'Oncologie Médicale, CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Polyclinique Francheville, Centre Catherine-de-Sienne [Nantes] (CCS), Centre Hospitalier Régional d'Orléans (CHRO), Hématologie clinique [CH Cholet], CH Cholet, Universität Heidelberg [Heidelberg], Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Tübingen [Germany], HESAM Université (HESAM)-HESAM Université (HESAM), University Hospital of Bonn, University of Innsbruck, Centre Hospitalier de Blois (CH Blois), Polyclinique Bordeaux Nord Aquitaine, Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Lille Nord de France (COMUE)-UNICANCER
Subjects: 0301 basic medicine, genetic structures, endocrine system diseases, [SDV]Life Sciences [q-bio], Gastroenterology, law.invention, Carboplatin, Polyethylene Glycols, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Ovarian Neoplasms, education.field_of_study, Standard treatment, Middle Aged, female genital diseases and pregnancy complications, 3. Good health, Bevacizumab, Oncology, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Austria, Female, France, medicine.drug, Adult, medicine.medical_specialty, Paclitaxel, Population, 03 medical and health sciences, Internal medicine, medicine, Fallopian Tube Neoplasms, Humans, education, Aged, Platinum, business.industry, Australia, eye diseases, Regimen, 030104 developmental biology, chemistry, Doxorubicin, sense organs, Neoplasm Recurrence, Local, business
Abstract: Background:\ud State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin–paclitaxel or carboplatin–gemcitabine) or the most active non-bevacizumab regimen: carboplatin–pegylated liposomal doxorubicin. The aim of this head-to-head trial was to compare a standard bevacizumab-containing regimen versus carboplatin–pegylated liposomal doxorubicin combined with bevacizumab.\ud Methods:\ud This multicentre, open-label, randomised, phase 3 trial, was done in 159 academic centres in Germany, France, Australia, Austria, and the UK. Eligible patients (aged ≥18 years) had histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with first disease recurrence more than 6 months after first-line platinum-based chemotherapy, and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were stratified by platinum-free interval, residual tumour, previous antiangiogenic therapy, and study group language, and were centrally randomly assigned 1:1 using randomly permuted blocks of size two, four, or six to receive six intravenous cycles of bevacizumab (15 mg/kg, day 1) plus carboplatin (area under the concentration curve [AUC] 4, day 1) plus gemcitabine (1000 mg/m 2, days 1 and 8) every 3 weeks or six cycles of bevacizumab (10 mg/kg, days 1 and 15) plus carboplatin (AUC 5, day 1) plus pegylated liposomal doxorubicin (30 mg/m 2, day 1) every 4 weeks, both followed by maintenance bevacizumab (15 mg/kg every 3 weeks in both groups) until disease progression or unacceptable toxicity. There was no masking in this open-label trial. The primary endpoint was investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy data were analysed in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug. This completed study is registered with ClinicalTrials.gov, NCT01837251.\ud Findings:\ud Between Aug 1, 2013, and July 31, 2015, 682 eligible patients were enrolled, of whom 345 were randomly assigned to receive carboplatin–pegylated liposomal doxorubicin–bevacizumab (experimental group) and 337 were randomly assigned to receive carboplatin–gemcitabine–bevacizumab (standard group). Median follow-up for progression-free survival at data cutoff (July 10, 2018) was 12·4 months (IQR 8·3–21·7) in the experimental group and 11·3 months (8·0–18·4) in the standard group. Median progression-free survival was 13·3 months (95% CI 11·7–14·2) in the experimental group versus 11·6 months (11·0–12·7) in the standard group (hazard ratio 0·81, 95% CI 0·68–0·96; p=0·012). The most common grade 3 or 4 adverse events were hypertension (88 [27%] of 332 patients in the experimental group vs 67 [20%] of 329 patients in the standard group) and neutropenia (40 [12%] vs 73 [22%]). Serious adverse events occurred in 33 (10%) of 332 patients in the experimental group and 28 (9%) of 329 in the standard group. Treatment-related deaths occurred in one patient in the experimental group (
Published: 2020
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48. Breast cancer risk and 6q22.33: combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2.

Author: Tomas Kirchhoff, Mia M Gaudet, Antonis C Antoniou, Lesley McGuffog, Manjeet K Humphreys, Alison M Dunning, Stig E Bojesen, Børge G Nordestgaard, Henrik Flyger, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Sei-Hyun Ahn, Thilo Dork, Peter Schürmann, Johann H Karstens, Peter Hillemanns, Fergus J Couch, Janet Olson, Celine Vachon, Xianshu Wang, Angela Cox, Ian Brock, Graeme Elliott, Malcolm W R Reed, Barbara Burwinkel, Alfons Meindl, Hiltrud Brauch, Ute Hamann, Yon-Dschun Ko, GENICA Network, Annegien Broeks, Marjanka K Schmidt, Laura J Van 't Veer, Linde M Braaf, Nichola Johnson, Olivia Fletcher, Lorna Gibson, Julian Peto, Clare Turnbull, Sheila Seal, Anthony Renwick, Nazneen Rahman, Pei-Ei Wu, Jyh-Cherng Yu, Chia-Ni Hsiung, Chen-Yang Shen, Melissa C Southey, John L Hopper, Fleur Hammet, Thijs Van Dorpe, Anne-Sophie Dieudonne, Sigrid Hatse, Diether Lambrechts, Irene L Andrulis, Natalia Bogdanova, Natalia Antonenkova, Juri I Rogov, Daria Prokofieva, Marina Bermisheva, Elza Khusnutdinova, Christi J van Asperen, Robert A E M Tollenaar, Maartje J Hooning, Peter Devilee, Sara Margolin, Annika Lindblom, Roger L Milne, José Ignacio Arias, M Pilar Zamora, Javier Benítez, Gianluca Severi, Laura Baglietto, Graham G Giles, kConFab, AOCS Study Group, Amanda B Spurdle, Jonathan Beesley, Xiaoqing Chen, Helene Holland, Sue Healey, Shan Wang-Gohrke, Jenny Chang-Claude, Arto Mannermaa, Veli-Matti Kosma, Jaana Kauppinen, Vesa Kataja, Bjarni A Agnarsson, Maria A Caligo, Andrew K Godwin, Heli Nevanlinna, Tuomas Heikkinen, Zachary Fredericksen, Noralane Lindor, Katherine L Nathanson, Susan M Domchek, SWE-BRCA, Niklas Loman, Per Karlsson, Marie Stenmark Askmalm, Beatrice Melin, Anna von Wachenfeldt, HEBON, Frans B L Hogervorst, Martijn Verheus, Matti A Rookus, Caroline Seynaeve, Rogier A Oldenburg, Marjolijn J Ligtenberg, Margreet G E M Ausems, Cora M Aalfs, Hans J P Gille, Juul T Wijnen, Encarna B Gómez García, EMBRACE, Susan Peock, Margaret Cook, Clare T Oliver, Debra Frost, Craig Luccarini, Gabriella Pichert, Rosemarie Davidson, Carol Chu, Diana Eccles, Kai-Ren Ong, Jackie Cook, Fiona Douglas, Shirley Hodgson, D Gareth Evans, Rosalind Eeles, Bert Gold, Paul D P Pharoah, Kenneth Offit, Georgia Chenevix-Trench, Douglas F Easton, and BCAC/CIMBA
Subjects: Medicine, Science
Abstract: Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p =
Published: 2012
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49. Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).

Author: Rebecca Hein, Melanie Maranian, John L Hopper, Miroslaw K Kapuscinski, Melissa C Southey, Daniel J Park, Marjanka K Schmidt, Annegien Broeks, Frans B L Hogervorst, H Bas Bueno-de-Mesquita, Kenneth R Muir, Artitaya Lophatananon, Suthee Rattanamongkongul, Puttisak Puttawibul, Peter A Fasching, Alexander Hein, Arif B Ekici, Matthias W Beckmann, Olivia Fletcher, Nichola Johnson, Isabel dos Santos Silva, Julian Peto, Elinor Sawyer, Ian Tomlinson, Michael Kerin, Nicola Miller, Frederick Marmee, Andreas Schneeweiss, Christof Sohn, Barbara Burwinkel, Pascal Guénel, Emilie Cordina-Duverger, Florence Menegaux, Thérèse Truong, Stig E Bojesen, Børge G Nordestgaard, Henrik Flyger, Roger L Milne, Jose Ignacio Arias Perez, M Pilar Zamora, Javier Benítez, Hoda Anton-Culver, Argyrios Ziogas, Leslie Bernstein, Christina A Clarke, Hermann Brenner, Heiko Müller, Volker Arndt, Christa Stegmaier, Nazneen Rahman, Sheila Seal, Clare Turnbull, Anthony Renwick, Alfons Meindl, Sarah Schott, Claus R Bartram, Rita K Schmutzler, Hiltrud Brauch, Ute Hamann, Yon-Dschun Ko, GENICA Network, Shan Wang-Gohrke, Thilo Dörk, Peter Schürmann, Johann H Karstens, Peter Hillemanns, Heli Nevanlinna, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, Natalia V Bogdanova, Iosif V Zalutsky, Natalia N Antonenkova, Marina Bermisheva, Darya Prokovieva, Albina Farahtdinova, Elza Khusnutdinova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana Hartikainen, Xiaoqing Chen, Jonathan Beesley, Kconfab Investigators, AOCS Group, Diether Lambrechts, Hui Zhao, Patrick Neven, Hans Wildiers, Stefan Nickels, Dieter Flesch-Janys, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Monica Barile, Fergus J Couch, Janet E Olson, Xianshu Wang, Zachary Fredericksen, Graham G Giles, Laura Baglietto, Catriona A McLean, Gianluca Severi, Kenneth Offit, Mark Robson, Mia M Gaudet, Joseph Vijai, Grethe Grenaker Alnæs, Vessela Kristensen, Anne-Lise Børresen-Dale, Esther M John, Alexander Miron, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L Andrulis, Julia A Knight, Gord Glendon, Anna Marie Mulligan, Jonine D Figueroa, Montserrat García-Closas, Jolanta Lissowska, Mark E Sherman, Maartje Hooning, John W M Martens, Caroline Seynaeve, Margriet Collée, Per Hall, Keith Humpreys, Kamila Czene, Jianjun Liu, Angela Cox, Ian W Brock, Simon S Cross, Malcolm W R Reed, Shahana Ahmed, Maya Ghoussaini, Paul D P Pharoah, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Anna Jakubowska, Katarzyna Jaworska, Katarzyna Durda, Elżbieta Złowocka, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Chen-Yang Shen, Jyh-Cherng Yu, Huan-Ming Hsu, Ming-Feng Hou, Nick Orr, Minouk Schoemaker, Alan Ashworth, Anthony Swerdlow, Amy Trentham-Dietz, Polly A Newcomb, Linda Titus, Kathleen M Egan, Georgia Chenevix-Trench, Antonis C Antoniou, Manjeet K Humphreys, Jonathan Morrison, Jenny Chang-Claude, Douglas F Easton, and Alison M Dunning
Subjects: Medicine, Science
Abstract: The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6 × 10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8 × 10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2 × 10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8 × 10(-9) in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8 × 10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3 × 10(-7), p(heterogeneity) = 5.1 × 10(-6)]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours.
Published: 2012
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50. Correction: Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).

Author: Rebecca Hein, Melanie Maranian, John L. Hopper, Miroslaw K. Kapuscinski, Melissa C. Southey, Daniel J. Park, Marjanka K. Schmidt, Annegien Broeks, Frans B. L. Hogervorst, H. Bas Bueno-de-Mesquit, Kenneth R. Muir, Artitaya Lophatananon, Suthee Rattanamongkongul, Puttisak Puttawibul, Peter A. Fasching, Alexander Hein, Arif B. Ekici, Matthias W. Beckmann, Olivia Fletcher, Nichola Johnson, Isabel dos Santos Silva, Julian Peto, Elinor Sawyer, Ian Tomlinson, Michael Kerin, Nicola Miller, Frederick Marmee, Andreas Schneeweiss, Christof Sohn, Barbara Burwinkel, Pascal Guénel, Emilie Cordina-Duverger, Florence Menegaux, Thérèse Truong, Stig E. Bojesen, Børge G. Nordestgaard, Henrik Flyger, Roger L. Milne, Jose Ignacio Arias Perez, M. Pilar Zamora, Javier Benítez, Hoda Anton-Culver, Argyrios Ziogas, Leslie Bernstein, Christina A. Clarke, Hermann Brenner, Heiko Müller, Volker Arndt, Christa Stegmaier, Nazneen Rahman, Sheila Seal, Clare Turnbull, Anthony Renwick, Alfons Meindl, Sarah Schott, Claus R. Bartram, Rita K. Schmutzler, Hiltrud Brauch, Ute Hamann, Yon-Dschun Ko, Shan Wang-Gohrke, Thilo Dörk, Peter Schürmann, Johann H. Karstens, Peter Hillemanns, Heli Nevanlinna, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, Natalia V. Bogdanova, Iosif V. Zalutsky, Natalia N. Antonenkova, Marina Bermisheva, Darya Prokovieva, Albina Farahtdinova, Elza Khusnutdinova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana Hartikainen, Xiaoqing Chen, Jonathan Beesley, kConFab Investigators, Diether Lambrechts, Hui Zhao, Patrick Neven, Hans Wildiers, Stefan Nickels, Dieter Flesch-Janys, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Monica Barile, Fergus J. Couch, Janet E. Olson, Xianshu Wang, Zachary Fredericksen, Graham G. Giles, Laura Baglietto, Catriona A. McLean, Gianluca Severi, Kenneth Offit, Mark Robson, Mia M. Gaudet, Joseph Vijai, Grethe Grenaker Alnæs, Vessela Kristensen, Anne-Lise Børresen-Dale, Esther M. John, Alexander Miron, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L. Andrulis, Julia A. Knight, Gord Glendon, Anna Marie Mulligan, Jonine D. Figueroa, Montserrat García-Closas, Jolanta Lissowska, Mark E. Sherman, Maartje Hooning, John W. M. Martens, Caroline Seynaeve, Margriet Collée, Per Hall, Keith Humpreys, Kamila Czene, Jianjun Liu, Angela Cox, Ian W. Brock, Simon S. Cross, Malcolm W. R. Reed, Shahana Ahmed, Maya Ghoussaini, Paul DP. Pharoah, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Anna Jakubowska, Katarzyna Jaworska, Katarzyna Durda, Elżbieta Złowocka, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Chen-Yang Shen, Jyh-Cherng Yu, Huan-Ming Hsu, Ming-Feng Hou, Nick Orr, Minouk Schoemaker, Alan Ashworth, Anthony Swerdlow, Amy Trentham-Dietz, Polly A. Newcomb, Linda Titus, Kathleen M. Egan, Georgia Chenevix-Trench, Antonis C. Antoniou, Manjeet K. Humphreys, Jonathan Morrison, Jenny Chang-Claude, Douglas F. Easton, and Alison M. Dunning
Subjects: Medicine, Science
Published: 2012
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