Author: "Sten Cornelissen" / Topic: medicine.medical_specialty - Searchworks@Jio Institute Digital Library Search Results

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1. Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma

Author: A.C.J. van Akkooi, Judith M. Versluis, Christian U. Blank, Charlotte L. Zuur, Elisa A. Rozeman, Willem M.C. Klop, Esmée P. Hoefsmit, Lindsay G Grijpink-Ongering, María Jesús González González, Sandra Adriaansz, Robyn P. M. Saw, Sydney Ch'ng, Sten Cornelissen, J Stretch, Annegien Broeks, Ton N. Schumacher, A A Torres Acosta, Hanna Eriksson, Ron M. Kerkhoven, B.A. van de Wiel, Petros Dimitriadis, Richard A. Scolyer, Oscar Krijgsman, Daniel S. Peeper, J.B.A.G. Haanen, Omgo E. Nieweg, Karolina Sikorska, Kerwin F. Shannon, Georgina V. Long, W.J. van Houdt, A.M. Menzies, H. Mallo, Irene L.M. Reijers, and Andrew J. Spillane
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, business.industry, Melanoma, Phases of clinical research, Ipilimumab, General Medicine, medicine.disease, General Biochemistry, Genetics and Molecular Biology, law.invention, Clinical trial, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Randomized controlled trial, law, 030220 oncology & carcinogenesis, Internal medicine, medicine, Adjuvant therapy, Biomarker (medicine), Nivolumab, business, medicine.drug
Abstract: Neoadjuvant ipilimumab plus nivolumab showed high pathologic response rates (pRRs) in patients with macroscopic stage III melanoma in the phase 1b OpACIN ( NCT02437279 ) and phase 2 OpACIN-neo ( NCT02977052 ) studies1,2. While the results are promising, data on the durability of these pathologic responses and baseline biomarkers for response and survival were lacking. After a median follow-up of 4 years, none of the patients with a pathologic response (n = 7/9 patients) in the OpACIN study had relapsed. In OpACIN-neo (n = 86), the 2-year estimated relapse-free survival was 84% for all patients, 97% for patients achieving a pathologic response and 36% for nonresponders (P
Published: 2021
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2. 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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3. P01.15 Personalized combination of neoadjuvant domatinostat, nivolumab (NIVO) and ipilimumab (IPI) in macroscopic stage III melanoma patients stratified according to interferon-gamma (IFN-gamma) signature – the DONIMI study

Author: Acj van Akkooi, A.M. Menzies, Ilm Reijers, Christian U. Blank, Elisa A. Rozeman, Richard A. Scolyer, Sten Cornelissen, Oscar Krijgsman, Judith M. Versluis, Georgina V. Long, Ljw Bosch, J Bouwman, Disha Rao, Petros Dimitriadis, Andrew J. Spillane, and B.A. van de Wiel
Subjects: Oncology, medicine.medical_specialty, business.industry, Ipilimumab, Clinical trial, Internal medicine, medicine, Clinical endpoint, Stage III melanoma, Dosing, Nivolumab, Adverse effect, business, Ifn gamma, medicine.drug
Abstract: Background The previous OpACIN and OpACIN-neo studies investigating neoadjuvant IPI plus NIVO have demonstrated high pathologic response rates (74–78%) and favorable long-term outcomes for patients (pts) with a pathological response; at 36 and 18 months follow up only 1/71 (1.4%) responders has relapsed. In contrast, pathological non-responders have a poor prognosis; 15/23 (65.2%) have relapsed so far. This emphasizes the need for baseline biomarkers predictive of non-response and new neoadjuvant treatment combinations for these pts. In our previous studies, baseline IFN-γ signature high pts were more likely to respond to IPI plus NIVO. The DONIMI study tests the combination of NIVO ± IPI combined with a class 1 histone deacetylase inhibitor, domatinostat (DOM), according to the pts IFN-γ signature. We have developed a neoadjuvant IFN-γ signature, based on the signature previously described by Ayers et al., that will be used for the first time to classify pts in this prospective trial. Trial design This two-center investigator-initiated phase 1b study aims to assess the safety and feasibility of neoadjuvant NIVO ± DOM ± IPI in 45 stage III melanoma pts with macroscopic de-novo or recurrent disease. IFN-γ signature high pts (n=20) will be randomized (stratified by center) to Arm A (2 cycles NIVO 240 mg q3wk) or Arm B (2 cycles NIVO 240 mg q3wk + DOM 200 mg twice daily (BID), d1-14, q3wk). IFN-γ signature low pts (n=25) will be randomized to Arm C (2 cycles NIVO 240 mg q3wk + DOM 200 mg BID, d1-14, q3wk) or Arm D (2 cycles NIVO 240 mg q3wk + IPI 80 mg q3wk + DOM 200 mg once daily (OD), d1-14, q3wk). Based on safety data of the first 5 pts in arm D, the remaining pts will be treated with either a higher dosing scheme (200 mg BID, d1-14, q3wks), a lower dosing scheme (100 mg OD, d1-14, q3wks) or the same dosing scheme (200 mg OD, d1-14, q3wks). The primary endpoint is safety and feasibility. A treatment arm will be declared as not feasible if 2/5 or 3/10 patients cannot adhere to the planned time of surgery (week 6 ± 1week) due to treatment-related adverse events. Biopsies (week 0, 3), blood samples (week 0, 3, 6, 12) and feces (week 0, 3, 6) will be collected for translational research. To date, 7 patients have been enrolled. Clinical trial information NCT04133948 Disclosure Information I.L.M. Reijers: None. E.A. Rozeman: None. P. Dimitriadis: None. O. Krijgsman: C. Other Research Support (supplies, equipment, receipt of drugs or other in-kind support); Modest; BMS. L.J.W. Bosch: None. S. Cornelissen: None. J. Bouwman: None. J.M. Versluis: None. D. Rao: None. B. van de Wiel: None. A.J. Spillane: None. R.A. Scolyer: F. Consultant/Advisory Board; Modest; MSD, Neracare, Myriad, Novartis. A.M. Menzies: F. Consultant/Advisory Board; Modest; BMS, MSD Oncology, Novartis, Pierre Fabre, Roche. A.C.J. van Akkooi: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Modest; Amgen, BMS, Novartis. F. Consultant/Advisory Board; Modest; Amgen, BMS, Novartis, MSD, Merck, Merck-Pfizer, 4SC. G.V. Long: F. Consultant/Advisory Board; Modest; Aduro, Amgen, BMS, Mass-Array, Pierre-Fabre, Novartis, Merck MSD, Roche. C.U. Blank: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Modest; BMS, Novartis, Nanostring. F. Consultant/Advisory Board; Modest; BMS, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, Genmab, Pierre Fabre.
Published: 2020
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4. LBA39 Personalized combination of neoadjuvant domatinostat, nivolumab (NIVO) and ipilimumab (IPI) in stage IIIB-D melanoma patients (pts) stratified according to the interferon-gamma signature (IFN-γ sign): The DONIMI study

Author: Petros Dimitriadis, Christian U. Blank, Richard A. Scolyer, Willem M.C. Klop, B.A. van de Wiel, A.C.J. van Akkooi, Irene L.M. Reijers, M.J.C. Gregorio, Andrew J. Spillane, Judith M. Versluis, Robert V. Rawson, Michel W.J.M. Wouters, Linda J.W. Bosch, G.V. Long, Sten Cornelissen, A.M. Menzies, Thomas E. Pennington, Marta Lopez-Yurda, Lindsay G Grijpink-Ongering, and Robyn P. M. Saw
Subjects: Oncology, medicine.medical_specialty, business.industry, Melanoma, Ipilimumab, Hematology, Stage iiib, medicine.disease, Internal medicine, medicine, Interferon gamma, Nivolumab, business, medicine.drug, Sign (mathematics)
Published: 2021
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5. A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer

Author: Harald Surowy, Rulla M. Tamimi, Javier Benitez, Wing-Yee Lo, Celine M. Vachon, Nadege Presneau, John J. Spinelli, Ann Smeets, Hoda Anton-Culver, Veli-Matti Kosma, Christopher A. Haiman, Martha J. Shrubsole, Ross L. Prentice, Diana Eccles, Ursula Eilber, Loic Le Marchand, Katri Pylkäs, Jirong Long, Michael P. Lux, Sara Margolin, Hedy S. Rennert, Tom Maishman, Mary B. Daly, Rita K. Schmutzler, Julian Peto, Sune F. Nielsen, Eric Hahnen, Niclas Håkansson, Børge G. Nordestgaard, Mitul Shah, Matthias W. Beckmann, Anthony J. Swerdlow, Barbara Burwinkel, Rudolf Kaaks, Usha Menon, William J. Tapper, Argyrios Ziogas, Peter Hillemanns, Fares Al-Ejeh, Roger L. Milne, Wolfgang Janni, Pascal Guénel, Mikael Eriksson, Clarice R. Weinberg, Kyriaki Michailidou, Jonathan Beesley, Marike Gabrielson, J. Esteban Castelao, Margriet Collée, Janet E. Olson, Gad Rennert, Per Broberg, Rob A. E. M. Tollenaar, David Cox, Paolo Peterlongo, Helian Feng, Brian D. Carter, Nichola Johnson, Emmanouil Saloustros, Dijana Plaseska-Karanfilska, Kimberly F. Doheny, Paul L. Auer, Hans Wildiers, Jacques Simard, Michael Untch, Per Hall, Martine Dumont, Julie M. Cunningham, Thilo Dörk, Mary Beth Terry, Jenny Chang-Claude, Lang Wu, Irene L. Andrulis, Xiaohong R. Yang, Caroline Baynes, Isabel dos-Santos-Silva, Douglas F. Easton, Wei Shi, Emily Hallberg, Camilla Wendt, Hiltrud Brauch, Diana Torres, Olufunmilayo I. Olopade, David Van Den Berg, Georgia Chenevix-Trench, Alfons Meindl, Stig E. Bojesen, Jonine D. Figueroa, Dale P. Sandler, Vessela N. Kristensen, Christine L. Clarke, Wei Zheng, Manuela Gago-Dominguez, E Rozali, Henrik Flyger, Sheila Seal, Guanmengqian Huang, Marjanka K. Schmidt, Håkan Olsson, Christopher G. Scott, Kamila Czene, Laura Fachal, Rodney J. Scott, Jennifer Stone, Sara Y. Brucker, Qin Wang, David J. Hunter, Maya Ghoussaini, Christoph Engel, Keith Humphreys, Susan M. Gapstur, Daniel C. Tessier, Paolo Radice, John L. Hopper, Audrey Y. Jung, Lucy Xia, Atocha Romero, Chenjie Zeng, Peter A. Fasching, Jan Lubinski, Anna González-Neira, Nazneen Rahman, Robert N. Hoover, Thérèse Truong, Fergus J. Couch, Anna Marie Mulligan, Robert J. MacInnis, Ute Hamann, Hanne Meijers-Heijboer, Brigitte Rack, Simon S. Cross, Federico Canzian, J.-P. Meyer, Sara Lindström, Natalia Bogdanova, Trinidad Caldés, Olivia Fletcher, Peter Kraft, Elinor J. Sawyer, Alexander Gusev, Louise A. Brinton, Diether Lambrechts, Bingshan Li, Kristan J. Aronson, Jane Romm, Anja Rudolph, Peter Devilee, Qiuyin Cai, Arto Mannermaa, Elad Ziv, Alice S. Whittemore, Abigail Thomas, Hermann Brenner, Montserrat Garcia-Closas, Patrick Neven, Kristine Jones, Miriam Dwek, Sibylle Loibl, Heli Nevanlinna, Jolanta Lissowska, Susan L. Neuhausen, Elza Khusnutdinova, Marina Bermisheva, Alicja Wolk, Lin Fritschi, Xingyi Guo, Angela Cox, Michael Jones, Xiaoqing Chen, Esther M. John, Richard Barfield, Volker Arndt, Patricia Harrington, Quinten Waisfisz, Daniel Vincent, Antoinette Hollestelle, Dimitrios Mavroudis, JoAnn E. Manson, Joe Dennis, Walter C. Willett, Stacey L. Edwards, Melissa C. Southey, Andreas Schneeweiss, Jack A. Taylor, Robert Winqvist, Mia M. Gaudet, David E. Goldgar, Anna Jakubowska, Paul D.P. Pharoah, Kathrin Thöne, Dieter Flesch-Janys, Mark S. Goldberg, Craig Luccarini, Sten Cornelissen, Jingmei Li, Michael J. Kerin, Myrto Barrdahl, Xiao-Ou Shu, Alison M. Dunning, Manjeet K. Bolla, Carl Blomqvist, Graham G. Giles, Hans Christiansen, A. Heather Eliassen, Valerie Rhenius, Alexander Hein, Belynda Hicks, Ivana Maleva Kostovska, Tongguang Cheng, Yingchang Lu, CCA - Cancer biology and immunology, Amsterdam Neuroscience - Complex Trait Genetics, Human genetics, Amsterdam Reproduction & Development (AR&D), Clinical Genetics, Medical Oncology, Guo, Xingyi [0000-0001-5269-1294], Al-Ejeh, Fares [0000-0002-1553-0077], Li, Bingshan [0000-0003-2129-168X], Gusev, Alexander [0000-0002-7980-4620], Andrulis, Irene L [0000-0002-4226-6435], Arndt, Volker [0000-0001-9320-8684], Brauch, Hiltrud [0000-0001-7531-2736], Collée, Margriet [0000-0002-9272-9346], Cox, Angela [0000-0002-5138-1099], Cunningham, Julie M [0000-0002-8159-3025], Fachal, Laura [0000-0002-7256-9752], Fletcher, Olivia [0000-0001-9387-7116], Hein, Alexander [0000-0003-2601-3398], Hicks, Belynda [0000-0001-8014-4888], Hollestelle, Antoinette [0000-0003-1166-1966], Jakubowska, Anna [0000-0002-5650-0501], Khusnutdinova, Elza [0000-0003-2987-3334], Li, Jingmei [0000-0001-8587-7511], Menon, Usha [0000-0003-3708-1732], Nevanlinna, Heli [0000-0002-0916-2976], Nordestgaard, Børge G [0000-0002-1954-7220], Pylkäs, Katri [0000-0002-2449-0521], Rennert, Gad [0000-0002-8512-068X], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Scott, Christopher G [0000-0003-1340-0647], Shrubsole, Martha J [0000-0002-5591-7575], Wolk, Alicja [0000-0001-7387-6845], Ziogas, Argyrios [0000-0003-4529-3727], Pharoah, Paul DP [0000-0001-8494-732X], Milne, Roger L [0000-0001-5764-7268], Easton, Douglas F [0000-0003-2444-3247], Zheng, Wei [0000-0003-1226-070X], Apollo - University of Cambridge Repository, Human Genetics, and ARD - Amsterdam Reproduction and Development
Subjects: 0301 basic medicine, Risk, medicine.medical_specialty, Gene Expression, Genome-wide association study, Breast Neoplasms, Biology, Genome-wide association studies, Polymorphism, Single Nucleotide, Article, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, Genetic model, Genetics, medicine, Humans, Genetic Predisposition to Disease, Genetic association, medicine.disease, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Case-Control Studies, Expression quantitative trait loci, Medical genetics, Female, Gene expression, Breast Cancer Genetics, Genome-Wide Association Study
Abstract: The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P −6, including 14 genes at loci not yet reported for breast cancer. We silenced 13 genes and showed an effect for 11 on cell proliferation and/or colony-forming efficiency. Our study provides new insights into breast cancer genetics and biology.
Published: 2019
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6. Personalized combination of neoadjuvant domatinostat, nivolumab and ipilimumab in macroscopic stage III melanoma patients stratified according to the interferon-gamma signature: The DONIMI study

Author: Alexander M. Menzies, Christian U. Blank, Sten Cornelissen, Bart A. van de Wiel, María Jesús González González, Richard A. Scolyer, Georgina V. Long, Linda J.W. Bosch, Lindsay G Grijpink-Ongering, Jasper Bouwman, Annegien Broeks, Petros Dimitriadis, Oscar Krijgsman, Alexander C.J. van Akkooi, Judith M. Versluis, Elisa A. Rozeman, Marloes van Dijk, Irene L.M. Reijers, Andrew J. Spillane, and Disha Rao
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, Ipilimumab, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Pathologic Response, Interferon gamma, Stage III melanoma, Nivolumab, business, 030215 immunology, medicine.drug
Abstract: TPS10087 Background: Previous OpACIN and OpACIN-neo studies, investigating neoadjuvant ipilimumab (IPI) plus nivolumab (NIVO), demonstrated high pathologic response rates (74-78%) and favorable long-term outcomes in patients (pts) achieving pathologic response; at 36 and 18 months follow-up, respectively, only 1/71 (1.4%) pts with response has relapsed. In contrast, pts without pathologic response (pNR) have a poor prognosis; 15/23 (65.2%) have relapsed so far. This emphasizes the need for baseline biomarkers predictive of non-response and new neoadjuvant treatment combinations for these pts. In our previous studies, baseline interferon-gamma (IFN-γ) signature low pts were less likely to respond to neoadjuvant IPI plus NIVO. The DONIMI study tests the combination of NIVO +/- IPI with domatinostat (DOM), a class 1 histone deacetylase inhibitor, according to the IFN-γ signature in the tumor. Based on the signature previously described by Ayers et al. we have developed a neoadjuvant IFN-γ signature algorithm that will be used for the first time to classify pts in this prospective trial. Methods: The aim of this two-center investigator-initiated phase 1b study is to assess the safety and feasibility of neoadjuvant NIVO +/- DOM +/- IPI in 45 stage III melanoma pts with RECIST 1.1 measurable de-novo or recurrent disease. IFN-γ signature high pts (n = 20) will be randomized (stratified by center) to Arm A (2 cycles NIVO 240mg q3wk) or Arm B (2 cycles NIVO 240mg q3wk + DOM 200mg twice daily (BID), d1-14, q3wk). IFN-γ signature low pts (n = 25) will be randomized to Arm C (2 cycles NIVO 240mg q3wk + DOM 200mg BID, d1-14, q3wk) or Arm D (2 cycles NIVO 240mg q3wk + IPI 80mg q3wk + DOM 200mg once daily (OD), d1-14, q3wk). Based on safety data of the first 5 pts in arm D, the remaining pts will be treated with either a higher dosing scheme (200mg BID, d1-14, q3wks), a lower dosing scheme (100mg OD, d1-14, q3wks) or the same dosing scheme (200mg OD, d1-14, q3wks). The primary endpoint is safety and feasibility. A treatment arm will be declared as not feasible if 2/5 or 3/10 pts cannot adhere to the preplanned time of surgery (week 6 +/- 1week) due to treatment-related adverse events. Biopsies (week 0, 3), blood samples (week 0, 3, 6, 12) and feces (week 0, 3, 6) will be collected for translational research. The first patient was enrolled on January 23th, 2020. Clinical trial information: NCT04133948.
Published: 2020
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7. Reproductive profiles and risk of breast cancer subtypes: a multi-center case-only study

Author: Javier Benitez, Sara Margolin, Diether Lambrechts, Alexandra J. van den Broek, Chen-Yang Shen, Veli-Matti Kosma, Matthias W. Beckmann, Siranoush Manoukian, Antoinette Hollestelle, Montserrat Garcia-Closas, Paul Brennan, Chiu-Chen Tseng, Marjanka K. Schmidt, Carolien H.M. van Deurzen, Peter A. Fasching, Melissa C. Southey, Manjeet K. Bolla, Robert Winqvist, Keitaro Matsuo, Douglas F. Easton, Carl Blomqvist, Adelheid Soubry, Paul D.P. Pharoah, Pascal Guénel, Jenna Lilyquist, Anna González-Neira, Hidemi Ito, Daehee Kang, Thérèse Truong, Fergus J. Couch, Renske Keeman, Kenneth Muir, Caroline Seynaeve, Katri Pylkäs, Simon S. Cross, Per Hall, Olivier Brouckaert, Roger L. Milne, Cheng Har Yip, Qin Wang, Sten Cornelissen, Anja Rudolph, Kamila Czene, Artitaya Lophatananon, Mikael Eriksson, Xiao-Ou Shu, Jonine D. Figueroa, Julia A. Knight, Arto Mannermaa, Jyh-Cherng Yu, Hans Wildiers, John L. Hopper, Wei Zheng, Jingmei Li, Rob A. E. M. Tollenaar, Anthony J. Swerdlow, Hermann Brenner, Henrik Flyger, Patrick Neven, Georgia Chenevix-Trench, Irene L. Andrulis, Paolo Peterlongo, Ji Yeob Choi, Annouschka Laenen, Annika Lindblom, Hiltrud Brauch, Anna H. Wu, Heli Nevanlinna, Michael Jones, Angela Cox, Volker Arndt, Soo-Hwang Teo, Jenny Chang-Claude, Stig E. Bojesen, Graham G. Giles, Suleeporn Saajrang, School of Medicine / Clinical Medicine, Wang, Jean [0000-0002-9139-0627], Benitez, Javier [0000-0002-0923-7202], Blomqvist, Carl [0000-0003-3041-1938], Brauch, Hiltrud [0000-0001-7531-2736], Brenner, Hermann [0000-0002-6129-1572], Chenevix-Trench, Georgia [0000-0002-1878-2587], Cox, Angela [0000-0002-5138-1099], Eriksson, Mikael [0000-0001-8135-4270], González-Neira, Anna [0000-0002-5421-2020], Guénel, Pascal [0000-0002-8359-518X], Jones, Michael [0000-0001-7479-3451], Li, Jingmei [0000-0001-8587-7511], Matsuo, Keitaro [0000-0003-1761-6314], Peterlongo, Paolo [0000-0001-6951-6855], Pylkäs, Katri [0000-0002-2449-0521], Southey, Melissa C [0000-0002-6313-9005], Swerdlow, Anthony [0000-0001-5550-4159], Truong, Thérèse [0000-0002-2943-6786], Pharoah, Paul [0000-0001-8494-732X], Easton, Douglas [0000-0003-2444-3247], Lambrechts, Diether [0000-0002-3429-302X], Apollo - University of Cambridge Repository, Medical Oncology, Pathology, Department of Oncology, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, HUS Comprehensive Cancer Center, Unión Europea. Comisión Europea. 7 Programa Marco, Cancer Research UK (Reino Unido), NIH - National Cancer Institute (NCI) (Estados Unidos), National Health and Medical Research Council (Australia), New South Wales Cancer Council (Reino Unido), Victorian Health Promotion Foundation, Dutch Cancer Society (Holanda), Agence Nationale de la Recherche (Francia), French Agency for Food, Environmental and Occupational Health & Safety (Francia), Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, Centro de Investigación Biomedica en Red - CIBER, Federal Ministry of Education & Research (Alemania), Cancer Society of Finland, Ministry of Education, Culture, Sports, Science, and Technology (Japón), Japan Agency for Medical Research and Development, United States Army Medical Research and Development Command, California Breast Cancer Research Program, German Cancer Aid, Ministry of Higher Education (Malasia), Biomedical Research Council (Singapore), National Institutes of Health (Estados Unidos), and National Research Foundation of Korea
Subjects: 0301 basic medicine, Oncology, Triple Negative Breast Neoplasms, Cohort Studies, 0302 clinical medicine, HORMONE-RECEPTOR STATUS, Medizinische Fakultät, Risk Factors, Odds Ratio, Young adult, Reproductive History, POPULATION, Age at menarche, education.field_of_study, WOMEN, ASSOCIATION, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Parity, PREGNANCY, 030220 oncology & carcinogenesis, Age at breast cancer diagnosis, kConFab, Menarche, Female, Cohort study, Research Article, Adult, medicine.medical_specialty, 3122 Cancers, Population, Breast Neoplasms, DIAGNOSIS, lcsh:RC254-282, Risk Assessment, MENARCHE, 1ST BIRTH, 03 medical and health sciences, Young Adult, AGE, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, Journal Article, medicine, Biomarkers, Tumor, Humans, ddc:610, education, Aged, Gynecology, Pregnancy, business.industry, Odds ratio, medicine.disease, 030104 developmental biology, Age at first full-time pregnancy, Breast cancer subtype, business
Abstract: Background Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis. Methods We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). In a case-only analysis, we used logistic regression to assess associations between reproductive factors and BC subtype compared to luminal A tumors as a reference. The interaction between age and parity in BC subtype risk was also tested, across all ages and, because age was modeled non-linearly, specifically at ages 35, 55 and 75 years. Results Parous women were more likely to be diagnosed with triple negative BC (TNBC) than with luminal A BC, irrespective of age (OR for parity = 1.38, 95% CI 1.16–1.65, p = 0.0004; p for interaction with age = 0.076). Parous women were also more likely to be diagnosed with luminal and non-luminal HER2-like BCs and this effect was slightly more pronounced at an early age (p for interaction with age = 0.037 and 0.030, respectively). For instance, women diagnosed at age 35 were 1.48 (CI 1.01–2.16) more likely to have luminal HER2-like BC than luminal A BC, while this association was not significant at age 75 (OR = 0.72, CI 0.45–1.14). While age at menarche was not significantly associated with BC subtype, increasing age at FFTP was non-linearly associated with TNBC relative to luminal A BC. An age at FFTP of 25 versus 20 years lowered the risk for TNBC (OR = 0.78, CI 0.70–0.88, p, published version, peerReviewed
Published: 2017
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8. Association analysis identifies 65 new breast cancer risk loci

Author: Michael Jones, Dong-Young Noh, Martha J. Shrubsole, Chen-Yang Shen, Xiaoqing Chen, Esther M. John, Patricia Harrington, Quinten Waisfisz, Sue K. Park, Miriam Dwek, Christa Stegmaier, Sibylle Loibl, Wing-Yee Lo, Suleeporn Sangrajrang, Susan L. Neuhausen, Marina Bermisheva, Alicja Wolk, Christof Sohn, Keun-Young Yoo, Arja Jukkola-Vuorinen, Kathrin Thöne, James McKay, John J. Spinelli, Brian D. Carter, Elza Khusnutdinova, Francois Bacot, Paul L. Auer, Anna H. Wu, Christopher I. Amos, Johanna I. Kiiski, Hans Wildiers, Manjeet K. Bolla, Soo Hwang Teo, Julie M. Cunningham, Zhaoming Wang, Dieter Flesch-Janys, Argyrios Ziogas, Ann Smeets, Min Hyuk Lee, Xiaohong R. Yang, Carl Blomqvist, Natalia Antonenkova, Vassilios Georgoulias, Siranoush Manoukian, Anne Lise Børresen-Dale, Montserrat Garcia-Closas, Priyanka Sharma, Michael J. Kerin, Loic Le Marchand, Yoshio Kasuga, Michael Untch, Thomas Brüning, Natalia Bogdanova, Juliet D. French, Mark E. Sherman, Diana Eccles, Don M. Conroy, Marcia Adams, Pascal Guénel, Jonine D. Figueroa, Somchai Thanasitthichai, Jonathan Beesley, Paolo Peterlongo, Angela Cox, Graham G. Giles, Hans Christiansen, Irene L. Andrulis, Caroline Baynes, V. Shane Pankratz, Kristine Jones, Wei Zheng, Motoki Iwasaki, Rita K. Schmutzler, Julian Peto, Sara Margolin, Hedy S. Rennert, Hidemi Ito, Caroline Seynaeve, Jirong Long, Rachel Lloyd, Mark S. Goldberg, Javier Benitez, Børge G. Nordestgaard, Kathleen E. Malone, A. Heather Eliassen, Valerie Rhenius, Kristan J. Aronson, Maartje J. Hooning, Ursula Eilber, Christopher A. Haiman, Ji Yeob Choi, Jaana M. Hartikainen, Ian W. Brock, Barbara Burwinkel, Brigitte Rack, Mitul Shah, Matthias W. Beckmann, Belynda Hicks, Bernardo Bonanni, Alexander Hein, Leslie Bernstein, Christine L. Clarke, Emilie Cordina-Duverger, Sabine Behrens, Hoda Anton-Culver, Angela Brooks-Wilson, Bin Zhu, Gord Glendon, Banu Arun, José A. García-Sáenz, Jose Ignacio Arias Perez, Anne Grundy, Ans M.W. van den Ouweland, Nadege Presneau, Volker Arndt, Mikael Eriksson, Simon S. Cross, Craig Luccarini, Anthony J. Swerdlow, Veli-Matti Kosma, Hui Miao, Ming-Feng Hou, Hiroji Iwata, Christi J. van Asperen, Henrik Flyger, Jennifer Stone, Qin Wang, Penny Soucy, Heli Nevanlinna, Jane Heyworth, Shoichiro Tsugane, Annika Lindblom, Curtis Olswold, Trinidad Caldés, Laura Fachal, Ed Dicks, Shirley Hui, Katja Butterbach, Alison M. Dunning, Peter Devilee, Qiuyin Cai, Antonis C. Antoniou, Diether Lambrechts, Katarzyna Kaczmarek, Katri Pylkäs, Fredrick R. Schumacher, Arif B. Ekici, Aaron D. Norman, Jolanta Lissowska, Daniel C. Tessier, N Hamel, Paolo Radice, Håkan Olsson, Vessela N. Kristensen, Ling Tong, Harald Surowy, Rulla M. Tamimi, Jonathan Tyrer, Michael P. Lux, Stacey L. Edwards, Kathryn J. Ruddy, Giske Ursin, Myrto Barrdahl, Xiao-Ou Shu, Primitiva Menéndez, Sara Y. Brucker, Elad Ziv, Kenneth Muir, Eric Hahnen, Andy C. H. Lee, Rodney J. Scott, Lothar Haeberle, Darya Prokofyeva, Isabel dos-Santos-Silva, Peter Kraft, David G. Cox, Jong Won Lee, Sunil R. Lakhani, Kelly-Anne Phillips, Douglas F. Easton, Melissa C. Southey, Jan Lubinski, Jose E. Castelao, Hanne Meijers-Heijboer, Ivana Maleva Kostovska, Siddhartha Kar, Renske Keeman, Celine M. Vachon, Diana Torres, Stephen J. Chanock, Jack A. Taylor, Emiel J. Th. Rutgers, Chuen Neng Lee, Jason Vollenweider, Gadi Rennert, Jane Romm, Amy E. McCart Reed, Kee Seng Chia, Thomas Rüdiger, Anja Rudolph, Catriona McLean, David Van Den Berg, Christopher G. Scott, Mervi Grip, Lucy Xia, Georgia Chenevix-Trench, Robert Winqvist, Mary Beth Terry, Jenny Chang-Claude, Hans-Ulrich Ulmer, Mikael Hartman, Dona N. Ho, Maria Kabisch, Christoph Engel, Claire Mulot, Grethe I. Grenaker Alnæs, Arto Mannermaa, Nazneen Rahman, Tjoung-Won Park-Simon, Atocha Romero, Lin Fritschi, Manuela Gago-Dominguez, Matthias Ruebner, Valerie Gaborieau, Keitaro Matsuo, Asha Rostamianfar, Emmanouil Saloustros, Dijana Plaseska-Karanfilska, J.-P. Meyer, Sara Lindström, Annegien Broeks, Audrey Lemaçon, Tsun Leung Chan, Tongguang Cheng, Robert J. MacInnis, Habibul Ahsan, Federico Canzian, Paul Brennan, Mia M. Gaudet, David E. Goldgar, Anna Jakubowska, Paul D.P. Pharoah, Jacek Gronwald, Sung-Won Kim, Daehee Kang, Daniel O. Stram, Nichola Johnson, Rob B. van der Luijt, Sten Cornelissen, Camilla Wendt, Dylan M. Glubb, Olufunmilayo I. Olopade, Usha Menon, David J. Hunter, Kristiina Aittomäki, Jamie Allen, Chiu-Chen Tseng, Keith Humphreys, Edmond S. K. Ma, Peter Hillemanns, Hiltrud Brauch, Chia-Ni Hsiung, Sheila Seal, Junko Ishiguro, Dale P. Sandler, Peter Schürmann, Gary D. Bader, Sarah Stewart-Brown, Flavio Lejbkowicz, Marike Gabrielson, Wolfgang Janni, Judith S. Brand, Jingmei Li, Ava Kwong, Stig E. Bojesen, Ying Zheng, Mila Pinchev, Yu Tang Gao, Susan E. Hankinson, Elinor J. Sawyer, Per Broberg, Sofia Khan, Grace Sheng, Alfons Meindl, Margriet Collée, Jyh-Cherng Yu, Ute Krüger, Louise A. Brinton, Elizabeth W. Pugh, Thilo Dörk, Hilary K. Finucane, Peter A. Fasching, Shan Wang-Gohrke, Jenna Lilyquist, Muriel A. Adank, Marjanka K. Schmidt, Susan M. Gapstur, Sune F. Nielsen, Maya Ghoussaini, Minouk J. Schoemaker, Roger L. Milne, Jacques Simard, Clarice R. Weinberg, Kyriaki Michailidou, Shivaani Mariapun, Rob A. E. M. Tollenaar, Lizet E. van der Kolk, Nicola Miller, Anna González-Neira, Ian Tomlinson, Thérèse Truong, Ross L. Prentice, Anna Marie Mulligan, Jason S. Carroll, Taiki Yamaji, Carolina Ellberg, Mingajeva Elvira, Olivia Fletcher, Arnaud Droit, Per Hall, Maria Elena Martinez, Maria Tengström, Hui Cai, Xia Jiang, Janet E. Olson, Julia A. Knight, Nick Orr, Angel Carracedo, Guanmengqian Huang, Martine Dumont, Cheng Har Yip, Tom Maishman, Mary B. Daly, Artitaya Lophatananon, Niclas Håkansson, Steven N. Hart, Nur Aishah Taib, Andreas Schneeweiss, Daniel F. Schmidt, Daniel Vincent, Antoinette Hollestelle, Dimitrios Mavroudis, JoAnn E. Manson, Joe Dennis, Walter C. Willett, Rudolf Kaaks, Karen McCue, Enes Makalic, Kimberly F. Doheny, Eunjung Lee, Robert N. Hoover, Fergus J. Couch, Ute Hamann, Alice S. Whittemore, Hermann Brenner, Lorraine Durcan, Kamila Czene, Patrick Neven, John L. Hopper, Clinical Genetics, Medical Oncology, Human Genetics, CCA - Cancer biology and immunology, Dennis, Joe [0000-0003-4591-1214], Wang, Jean [0000-0002-9139-0627], Tyrer, Jonathan [0000-0003-3724-4757], Dicks, Ed [0000-0002-0617-0401], Lee, Andrew [0000-0003-0677-0252], Allen, Jamie [0000-0002-8677-2225], Fachal Vilar, Laura [0000-0002-7256-9752], Carroll, Jason [0000-0003-3643-0080], Rhenius, Valerie [0000-0003-4215-3235], Antoniou, Antonis [0000-0001-9223-3116], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, and Amsterdam Reproduction & Development (AR&D)
Subjects: 0301 basic medicine, Multifactorial Inheritance, Genome-wide association study, Regulatory Sequences, Nucleic Acid, skin and connective tissue diseases, Cancer genetics, Genetics, Multidisciplinary, medicine.diagnostic_test, 3. Good health, Europe, annotation, Medical genetics, Female, Asian Continental Ancestry Group, medicine.medical_specialty, Asia, architecture, European Continental Ancestry Group, ABCTB Investigators, Locus (genetics), Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, Risk Assessment, Article, White People, NBCS Collaborators, 03 medical and health sciences, Breast cancer, Asian People, SDG 3 - Good Health and Well-being, Genetic variation, ConFab/AOCS Investigators, expression, medicine, Genetic predisposition, Journal Article, Humans, Computer Simulation, Genetic Predisposition to Disease, biological pathways, Genetic association, Genetic testing, Genetic association study, Binding Sites, interaction networks, medicine.disease, comprehensive molecular portraits, mutations, susceptibility loci, 030104 developmental biology, Genetic Loci, genome-wide association, protein, Transcription Factors, Genome-Wide Association Study
Abstract: Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P
Published: 2017
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9. Evaluation of the EGFR polymorphism R497K in two cohorts of neoadjuvantly treated breast cancer patients

Author: Lennart Mulder, Hayra de Andrade Vieira-Monteiro, Esther H. Lips, Marjanka K. Schmidt, Jelle Wesseling, Marcelo Sobral-Leite, Daniely Regina Freitas-Alves, Rosane Vianna-Jorge, Sten Cornelissen, and Letícia Carlos Giacomin
Subjects: 0301 basic medicine, Oncology, Heredity, medicine.medical_treatment, Cancer Treatment, lcsh:Medicine, Geographical locations, Cohort Studies, 0302 clinical medicine, Genotype, Antineoplastic Combined Chemotherapy Protocols, Breast Tumors, Medicine and Health Sciences, Epidermal growth factor receptor, lcsh:Science, Multidisciplinary, Invasive carcinoma, biology, Pharmaceutics, ErbB Receptors, Genetic Mapping, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Cohort, Female, Lymph, Anatomy, Brazil, Research Article, medicine.medical_specialty, Breast Neoplasms, Variant Genotypes, Surgical and Invasive Medical Procedures, Lymphatic System, 03 medical and health sciences, Breast cancer, Drug Therapy, Diagnostic Medicine, Internal medicine, Breast Cancer, medicine, Genetics, Cancer Detection and Diagnosis, Humans, Chemotherapy, Pathological, Polymorphism, Genetic, business.industry, lcsh:R, Biology and Life Sciences, Cancers and Neoplasms, South America, medicine.disease, 030104 developmental biology, biology.protein, lcsh:Q, Lymph Nodes, People and places, business
Abstract: Pathological response of breast cancer to neoadjuvant chemotherapy (NAC) presents great variability, and new prognostic biomarkers are needed. Our aim was to evaluate the association of the epidermal growth factor receptor gene (EGFR) polymorphism R497K (rs2227983) with prognostic features and clinical outcomes of breast cancer, including the pathological response to NAC and the recurrence-free survival (RFS). Tumoral complete response (tCR) was defined by no remaining invasive cancer in the excised breast, whereas pathological complete response (pCR) was defined by no remaining invasive cancer both in the excised breast and lymph nodes. Two independent cohorts were analyzed: one from Brazil (INCA, n = 288) and one from The Netherlands (NKI-AVL, n = 255). In the INCA cohort, the variant (Lys-containing) genotypes were significantly associated with lower proportion of tCR (ORadj = 0.92; 95%CI = 0.85–0.99), whereas in the NKI-AVL cohort they were associated with tumor grade 3 (p = 0.035) and with triple-negative subtype (p = 0.032), but not with clinical outcomes. Such distinct prognostic associations may have arisen due to different neoadjuvant protocols (p < 0.001), or to lower age at diagnosis (p < 0.001) and higher proportion of tumor grade 3 (p = 0.018) at the NKI-AVL cohort. Moreover, NKI-AVL patients achieved better proportion of pCR (21.2% vs 8.3%, p < 0.001) and better RFS (HRadj = 0.48; 95% adjCI = 0.26–0.86) than patients from INCA. In conclusion, large scale studies comprehending different populations are needed to evaluate the impact of genome variants on breast cancer outcomes.
Published: 2017

10. Age- and Tumor Subtype Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers

Author: Sten Cornelissen, Richard van Hien, Muriel A. Adank, Argyrios Ziogas, Amy Trentham-Dietz, Frans B. L. Hogervorst, Hiltrud Brauch, Alison M. Dunning, Qin Wang, Stig E. Bojesen, Natalia Bogdanova, Hoda Anton-Culver, Sara Margolin, Elza Khusnutdinova, Marjanka K. Schmidt, Elinor J. Sawyer, Kenneth Offit, Lothar Haeberle, Veli-Matti Kosma, Natalia Antonenkova, Taru A. Muranen, Heli Nevanlinna, Polly A. Newcomb, Manjeet K. Bolla, Mieke Schutte, Vessela N. Kristensen, Andy C. H. Lee, Melissa C. Southey, Jenny Chang-Claude, Douglas F. Easton, Marina Bermisheva, Henrik Flyger, Lizet E. van der Kolk, Antonis C. Antoniou, Anna Jakubowska, Paul D.P. Pharoah, Ans M.W. van den Ouweland, Jan Lubinski, Angela Cox, Maartje J. Hooning, Graham G. Giles, Rita K. Schmutzler, Julian Peto, Anthony J. Swerdlow, Volker Arndt, Thilo Dörk, Barbara Burwinkel, Harald Surowy, Ian Tomlinson, Celine M. Vachon, Peter Hillemanns, Mark E. Robson, Michael Jones, Roger L. Milne, Esther M. John, Olivia Fletcher, Julie Soens, Per Hall, Quinten Waisfisz, Jonine D. Figueroa, Julia A. Knight, Rob A. E. M. Tollenaar, Irene L. Andrulis, Annika Lindblom, Annegien Broeks, Alfons Meindl, Peter A. Fasching, Montserrat Garcia-Closas, Georgia Chenevix-Trench, Thomas Brüning, Alice S. Whittemore, Caroline M. Seynaeve, Tjoung-Won Park-Simon, Eva Galle, Hermann Brenner, Hanne Meijers, Amanda B. Spurdle, Antoinette Hollestelle, Kamila Czene, Anja Rudolph, John L. Hopper, Arto Mannermaa, Simon S. Cross, Fergus J. Couch, Human genetics, CCA - Cancer biology, Antoniou, Antonis [0000-0001-9223-3116], Dunning, Alison [0000-0001-6651-7166], Lee, Andrew [0000-0003-0677-0252], Pharoah, Paul [0000-0001-8494-732X], Wang, Jean [0000-0002-9139-0627], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Clinical Genetics, and Medical Oncology
Subjects: 0301 basic medicine, Oncology, Cancer Research, Estrogen receptor, Disease, 0302 clinical medicine, Receptors, 80 and over, Odds Ratio, 2.1 Biological and endogenous factors, Aetiology, skin and connective tissue diseases, Progesterone, Cancer, Sequence Deletion, Aged, 80 and over, education.field_of_study, Homozygote, Age Factors, ORIGINAL REPORTS, Middle Aged, 3. Good health, Receptors, Estrogen, 030220 oncology & carcinogenesis, Female, Risk assessment, Receptors, Progesterone, Adult, medicine.medical_specialty, Heterozygote, Clinical Sciences, Oncology and Carcinogenesis, Population, Breast Neoplasms, Risk Assessment, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Clinical Research, Internal medicine, Breast Cancer, Genetics, medicine, Humans, Genetic Predisposition to Disease, Oncology & Carcinogenesis, education, CHEK2, Aged, business.industry, Case-control study, Odds ratio, medicine.disease, Estrogen, Checkpoint Kinase 2, 030104 developmental biology, Case-Control Studies, business
Abstract: Purpose CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC. Patients and Methods CHEK2*1100delC genotyping was mostly done by a custom Taqman assay. Breast cancer odds ratios (ORs) for CHEK2*1100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies. Results Proportions of heterozygous CHEK2*1100delC carriers in controls, in patients with breast cancer from population- and hospital-based studies, and in patients with breast cancer from familial- and clinical genetics center–based studies were 0.5%, 1.3%, and 3.0%, respectively. The estimated OR for invasive breast cancer was 2.26 (95%CI, 1.90 to 2.69; P = 2.3 × 10−20). The OR was higher for estrogen receptor (ER)–positive disease (2.55 [95%CI, 2.10 to 3.10; P = 4.9 × 10−21]) than it was for ER-negative disease (1.32 [95%CI, 0.93 to 1.88; P = .12]; P interaction = 9.9 × 10−4). The OR significantly declined with attained age for breast cancer overall (P = .001) and for ER-positive tumors (P = .001). Estimated cumulative risks for development of ER-positive and ER-negative tumors by age 80 in CHEK2*1100delC carriers were 20% and 3%, respectively, compared with 9% and 2%, respectively, in the general population of the United Kingdom. Conclusion These CHEK2*1100delC breast cancer risk estimates provide a basis for incorporating CHEK2*1100delC into breast cancer risk prediction models and into guidelines for intensified screening and follow-up.
Published: 2016
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11. 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium

Author: Javier Benitez, Frederik Marmé, Nichola Johnson, Ian W. Brock, Fiona M. Blows, Natalia Bogdanova, Arto Mannermaa, Peter Hillemanns, Hoda Anton-Culver, Anthony J. Swerdlow, Roger L. Milne, Jonathan Beesley, Veli-Matti Kosma, Guzel Zinnatullina, Paolo Peterlongo, Irene L. Andrulis, Annika Lindblom, Dieter Flesch-Janys, Ann Smeets, Arif B. Ekici, Pascal Guénel, Vesa Kataja, Thomas Brüning, Graham G. Giles, Isabel dos-Santos-Silva, Douglas F. Easton, Yuriy Rogov, Ruediger Schulz-Wendtland, Pierre Laurent-Puig, Thilo Dörk, Malcolm W.R. Reed, Heiko Müller, Linda M. Braaf, Janet E. Olson, Cariona A. McLean, Leslie Bernstein, Elinor J. Sawyer, Jaana M. Hartikainen, Siranoush Manoukian, Robert Paridaens, Marina Bermisheva, Natalia Antonenkova, Ian Tomlinson, Thérèse Truong, Minouk J. Schoemaker, Anna Marie Mulligan, Elza Khusnutdinova, Xianshu Wang, Christof Sohn, Katri Pylkäs, Caroline M. Seynaeve, Christina Clarke Dur, Caroline Weltens, Sune F. Nielsen, Carl Blomqvist, Nick Orr, Hiltrud Brauch, Maryam Mahmoodi, Shan Wang-Gohrke, Melissa C. Southey, Fergus J. Couch, Olivia Fletcher, Mervi Grip, Nayana Weerasooriya, Georgia Chenevix-Trench, Rita K. Schmutzler, Julian Peto, Jenny Chang-Claude, Peter Schürmann, Frank Dudbridge, John W.M. Martens, Robert Winqvist, Surapon Wiangnon, Celine M. Vachon, Arkom Chaiwerawattana, Hermann Brenner, Artitaya Lophatananon, Arja Jukkola-Vuorinen, Peter A. Fasching, Børge G. Nordestgaard, Manjeet K. Humphreys, Barbara Burwinkel, Kristiina Aittomäki, Marjanka K. Schmidt, Argyrios Ziogas, Michael Bremer, Paul D.P. Pharoah, Loris Bernard, Alexander Miron, Sara Margolin, Kamila Czene, Diether Lambrechts, Claus R. Bartram, Annegien Broeks, Maya Ghoussaini, John L. Hopper, Simon S. Cross, Matthias W. Beckmann, Per Hall, Agnes Jager, Stig E. Bojesen, Michael Jones, Darya Prokofyeva, Julia A. Knight, Alan Ashworth, Taru A. Muranen, Xiaoqing Chen, Esther M. John, Claire Mulot, Alfons Meindl, Ursula Eilber, Laura Baglietto, José Ignacio Arias-Perez, Peter Devilee, Henrik Flyger, Sten Cornelissen, Jingmei Li, Katharina Buck, Carmel Apicella, Michael J. Kerin, Gianluca Severi, Alison M. Dunning, Kenneth Muir, Anne Langheinz, Andreas Schneeweiss, Heli Nevanlinna, Michael Golatta, Christina Justenhoven, Antoinette Hollestelle, Jianjun Liu, Helen R. Warren, Sabine Behrens, Madeleine M.A. Tilanus-Linthorst, Angela Cox, Maartje J. Hooning, Qin Wang, Paolo Radice, Volker Arndt, Robert A.E.M. Tollenaar, M. Pilar Zamora, Medical Oncology, Surgery, and Clinical Genetics
Subjects: Oncology, Pathology, Epidemiology, Estrogen receptor, population, Genome-wide association study, genetic risk, 0302 clinical medicine, Receptors, common variants, Progesterone, 0303 health sciences, education.field_of_study, identifies 2, Chromosome Mapping, Single Nucleotide, Middle Aged, 5p12, 3. Good health, Receptors, Estrogen, 030220 oncology & carcinogenesis, alleles, Female, Chromosomes, Human, Pair 9, Receptors, Progesterone, linkage, Human, Pair 9, medicine.medical_specialty, Population, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, Chromosomes, Article, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Polymorphism, Allele, education, Aged, 030304 developmental biology, menarche, Case-control study, Cancer, medicine.disease, confer susceptibility, Estrogen, Case-Control Studies, genome-wide association, Genome-Wide Association Study
Abstract: Background: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). Methods: To further investigate the rs865686–breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case–control studies (48,394 cases, 50,836 controls). Results: This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P = 2.01 × 10−29] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (Phet) = 1.3 × 10−143], but no evidence of ethnic differences in per allele OR (Phet = 0.43). rs865686 was associated with estrogen receptor–positive (ER+) disease (per G-allele OR, 0.89; 95% CI, 0.86–0.91; P = 3.13 × 10−22) but less strongly, if at all, with ER-negative (ER−) disease (OR, 0.98; 95% CI, 0.94–1.02; P = 0.26; Phet = 1.16 × 10−6), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the G allele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER+ tumors. Conclusions: This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer. Impact: The findings further support the view that genetic susceptibility varies according to tumor subtype. Cancer Epidemiol Biomarkers Prev; 21(10); 1783–. ©2012 AACR.
Published: 2016

12. 11q13 is a susceptibility locus for hormone receptor positive breast cancer

Author: Dong Young Noh, Pascal Guénel, Graeme Elliott, Vesa Kataja, Shamil Gancev, Xianshu Wang, Shan Wang-Gohrke, Annegien Broeks, Florence Menegaux, Hans Wildiers, Richard van Hien, Natalia Bogdanova, Jean Wang, Puttisak Puttawibul, Betül T. Yesilyurt, Peter Devilee, Gord Glendon, Katri Pylkäs, Mark E. Sherman, Jenny Chang-Claude, Federik Marme, Michael Bremer, Katarzyna Durda, Sarah Schott, Vessela N. Kristensen, Paolo Radice, Teresa Selander, Kamila Czene, Alfons Meindl, Gianluca Severi, Angela Cox, Maartje J. Hooning, Claus R. Bartram, John L. Hopper, Ursel Eilber, Michael Jones, M. Pilar Zamora, Stephen J. Chanock, Laura Baglietto, Caroline M. Seynaeve, Daehee Kang, Thilo Dörk, Rita K. Schmutzler, Julian Peto, Børge G. Nordestgaard, Loris Bernard, Stig E. Bojesen, Barbara Burwinkel, Douglas F. Easton, Arif B. Ekici, kConFab Investigators, Mervi Grip, Robert A.E.M. Tollenaar, Argyrios Ziogas, Jonathan Beesley, Paolo Peterlongo, Volker Arndt, Xiaoqing Chen, Nichola Johnson, Jaana M. Hartikainen, Ming-Feng Hou, Diether Lambrechts, Ruediger Schulz-Wendtland, Jan Lubinski, Taru A. Muranen, Heli Nevanlinna, Esther M. John, Graham G. Giles, Chen-Yang Shen, Jolanta Lissowska, Ian W. Brock, Grethe I. Grenaker Alnæs, Gillian S. Dite, Charlotte Lanng, Hiltrud Brauch, Anthony J. Swerdlow, MC Southey, Christina Justenhoven, Manjeet K. Humphreys, Keun-Young Yoo, Elinor J. Sawyer, Emilie Cordina-Duverger, Jose Ignacio Arias Perez, Fergus J. Couch, Peter Schürmann, Stefan Nickels, Jianjun Liu, Marjanka K. Schmidt, Zachary S. Fredericksen, Yuri I. Rogov, Ute Hamann, Elza Khusnutdinova, Hermann Brenner, Sara Margolin, Natalia Antonenkova, Peter A. Fasching, Matthias W. Beckmann, Johann H. Karstens, Montserrat Garcia-Closas, Patrick Neven, Thomas Brüning, Carl Blomqvist, Heiko Müller, Jyh Cherng Yu, Katarzyna Jaworska, Yon Ko, Pei Ei Wu, Arto Mannermaa, Rebecca Hein, Darya Prokofieva, Melissa C. Southey, Andreas Schneeweiss, Irene L. Andrulis, Christa Stegmaier, Robert Winqvist, Annika Lindblom, Anna Jakubowska, Paul D.P. Pharoah, Peter Hillemanns, Alexander Miron, Roger L. Milne, Marina Bermisheva, Dieter Flesch-Janys, Christof Sohn, Nicola Miller, Georgia Chenevix-Trench, Kristiina Aittomäki, Ian Tomlinson, Thérèse Truong, Anna Marie Mulligan, Siranoush Manoukian, Robert Paridaens, Anne Lise Børresen-Dale, Suthee Rattanamongkongul, Olivia Fletcher, Simon S. Cross, Artitaya Lophatananon, Isabel dos Santos Silva, Janet E. Olson, Nick Orr, Per Hall, Alan Ashworth, Javier Benitez, Hoda Anton-Culver, Veli-Matti Kosma, Alison M. Dunning, Kenneth Muir, Sten Cornelissen, Carmel Apicella, Arja Jukkola-Vuorinen, Michael J. Kerin, ~, and Medical Oncology
Subjects: Oncology, hormone receptor status, Estrogen receptor, Genome-wide association study, 0302 clinical medicine, Risk Factors, Genotype, Receptors, single-nucleotide polymorphisms, common variants, Pair 11, Progesterone, Genetics (clinical), Genetics, 0303 health sciences, repair genes, Single Nucleotide, identifies 5, 11q13, Breast cancer susceptibility, Genome-wide association, Hormone receptor status, Polymorphisms, Risk factors, Breast Neoplasms, Chromosomes, Human, Pair 11, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Receptors, Estrogen, Receptors, Progesterone, 3. Good health, ovarian-cancer, 030220 oncology & carcinogenesis, Human, brca1 mutations, medicine.medical_specialty, Single-nucleotide polymorphism, Biology, Chromosomes, Article, White People, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, Progesterone receptor, medicine, Polymorphism, 030304 developmental biology, breast cancer susceptibility, Odds ratio, tumor characteristics, medicine.disease, confer susceptibility, Estrogen, genome-wide association, family registry, Ovarian cancer, polymorphisms
Abstract: Journal article A recent two-stage genome-wide association study (GWAS) identified five novel breast cancer susceptibility loci on chromosomes 9, 10, and 11. To provide more reliable estimates of the relative risk associated with these loci and investigate possible heterogeneity by subtype of breast cancer, we genotyped the variants rs2380205, rs1011970, rs704010, rs614367, and rs10995190 in 39 studies from the Breast Cancer Association Consortium (BCAC), involving 49,608 cases and 48,772 controls of predominantly European ancestry. Four of the variants showed clear evidence of association (P â ¤ 3 Ã 10(-9) ) and weak evidence was observed for rs2380205 (P = 0.06). The strongest evidence was obtained for rs614367, located on 11q13 (per-allele odds ratio 1.21, P = 4 Ã 10(-39) ). The association for rs614367 was specific to estrogen receptor (ER)-positive disease and strongest for ER plus progesterone receptor (PR)-positive breast cancer, whereas the associations for the other three loci did not differ by tumor subtype. EC Seventh Framework Programme - grant number HEALTH-F2-2009-223175 peer-reviewed
Published: 2016
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13. Impact of Age at Primary Breast Cancer on Contralateral Breast Cancer Risk in BRCA1/2 Mutation Carriers

Author: Mike van Beek, Maryska L.G. Janssen-Heijnen, Cees J. Cornelisse, Vincent T.H.B.M. Smit, Pieter J. Westenend, Laura J. van't Veer, Maartje J. Hooning, Rob A. E. M. Tollenaar, Alexandra J. van den Broek, Caroline Seynaeve, Sten Cornelissen, Marjanka K. Schmidt, Sabine Siesling, Jan J. Jobsen, Annegien Broeks, Flora E. van Leeuwen, Emiel J. Th. Rutgers, Health Technology & Services Research, and Medical Oncology
Subjects: 0301 basic medicine, Oncology, Adult, Cancer Research, medicine.medical_specialty, Heterozygote, endocrine system diseases, DNA Mutational Analysis, Breast Neoplasms, Risk Assessment, Contralateral breast cancer, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Prevalence, Humans, Genetic Predisposition to Disease, skin and connective tissue diseases, Neoplasm Staging, Netherlands, Retrospective Studies, BRCA2 Protein, business.industry, BRCA1 Protein, Hazard ratio, Age Factors, Retrospective cohort study, Neoplasms, Second Primary, Middle Aged, medicine.disease, Prognosis, 030104 developmental biology, 030220 oncology & carcinogenesis, Cohort, Mutation, Population study, Female, business, Risk assessment, Primary breast cancer, Follow-Up Studies
Abstract: Purpose To determine prospectively overall and age-specific estimates of contralateral breast cancer (CBC) risk for young patients with breast cancer with or without BRCA1/2 mutations. Patients and Methods A cohort of 6,294 patients with invasive breast cancer diagnosed under 50 years of age and treated between 1970 and 2003 in 10 Dutch centers was tested for the most prevalent BRCA1/2 mutations. We report absolute risks and hazard ratios within the cohort from competing risk analyses. Results After a median follow-up of 12.5 years, 578 CBCs were observed in our study population. CBC risk for BRCA1 and BRCA2 mutation carriers was two to three times higher than for noncarriers (hazard ratios, 3.31 [95% CI, 2.41 to 4.55; P < .001] and 2.17 [95% CI,1.22 to 3.85; P = .01], respectively). Ten-year cumulative CBC risks were 21.1% (95% CI, 15.4 to 27.4) for BRCA1, 10.8% (95% CI, 4.7 to 19.6) for BRCA2 mutation carriers and 5.1% (95% CI, 4.5 to 5.7) for noncarriers. Age at diagnosis of the first breast cancer was a significant predictor of CBC risk in BRCA1/2 mutation carriers only; those diagnosed before age 41 years had a 10-year cumulative CBC risk of 23.9% (BRCA1: 25.5%; BRCA2: 17.2%) compared with 12.6% (BRCA1: 15.6%; BRCA2: 7.2%) for those 41 to 49 years of age (P = .02); our review of published studies showed ranges of 24% to 31% before age 40 years (BRCA1: 24% to 32%; BRCA2:17% to 29%) and 8% to 21% after 40 years (BRCA1: 11% to 52%; BRCA2: 7% to 18%), respectively. Conclusion Age at first breast cancer is a strong risk factor for cumulative CBC risk in BRCA1/2 mutation carriers. Considering the available evidence, age-specific risk estimates should be included in counseling.
Published: 2016

14. Refined histopathological predictors of BRCA1 and BRCA2mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Author: Rongxi Yang, Hoda Anton-Culver, Dieter Flesch-Janys, Veli-Matti Kosma, Alexander Miron, Siranoush Manoukian, Giulietta Scuvera, Sten Cornelissen, Fergus J. Couch, Beth Y. Karlan, Janet E. Olson, Katarzyna Durda, Muhammad Usman Rashid, Diana Eccles, Debra Frost, Antonis C. Antoniou, William J. Tapper, José Ignacio Arias, Madeleine M. A. Tilanus-Linthorst, Ute Hamann, Sara Margolin, Thilo Dörk, Pilar Zamora, Sune F. Nielsen, Laura Papi, Radka Platte, Fabio Capra, Marjanka K. Schmidt, Matthias W. Beckmann, Peter A. Fasching, Tjoung Won Park-Simon, Lesley McGuffog, Alfons Meindl, Amanda B. Spurdle, Barbara Wappenschmidt, Katherine L. Nathanson, Bernardo Bonanni, Christine L. Clarke, Julian Adlard, Fiona M. Blows, Arja Jukkola-Vuorinen, Isabel dos-Santos-Silva, Catriona McLean, Georgia Chenevix-Trench, Frederique Mariette, Malcolm W.R. Reed, Douglas F. Easton, Vesa Kataja, Frederik Marmé, Laura Baglietto, Christopher A. Haiman, Monica Barile, Uffe Birk Jensen, Thomas Brüning, Shan Wang-Gohrke, Thomas Rüdiger, Paolo Radice, Alessandra Viel, Annegien Broeks, Dee W. West, Loic Le Marchand, Mary Beth Terry, Jenny Chang-Claude, Lorraine Durcan, Raymonda Varon-Mateeva, Brian E. Henderson, Robert A.E.M. Tollenaar, Hansjoerg Plendl, Katri Pylkäs, Jane Carpenter, Mads Thomassen, Kenneth Offitt, Sabine Preisler-Adams, Dennis J. Slamon, Kamila Czene, D. Gareth Evans, Senno Verhoef, Jonine Figueroa, Anja Rudolph, Kristiina Aittomäki, Arto Mannermaa, Eric Hahnen, Jacek Gronwald, Aida Karina Dieffenbach, Johanna Rantala, Ruth Swann, Paolo Peterlongo, Melissa C. Southey, Liliana Varesco, Katarzyna Jaworska-Bieniek, Elena Provenzano, Henrik Flyger, Hiltrud Brauch, Trevor Cole, Alison M. Dunning, Sue Healey, Robert Winqvist, Soo Hwang Teo, Rachel E. Factor, Timothy R. Rebbeck, Jaana M. Hartikainen, Irene L. Andrulis, Louise Jones, Rosemary L. Balleine, Gord Glendon, Doris Steinemann, David E. Goldgar, Anna Jakubowska, Paul D.P. Pharoah, Miriam Dwek, Heli Nevanlinna, Karin Kast, Nichola Johnson, Stefano Fortuzzi, Argyrios Ziogas, John W.M. Martens, Christa Stegmaier, Vernon S. Pankratz, Peter Devilee, Thomas Hansen, Christian Sutter, Vijai Joseph, Ana Osorio, Harald Surovy, Päivi Heikkilä, Kerstin Rhiem, Fredrick R. Schumacher, Susan L. Neuhausen, Michael T. Parsons, Jolanta Lissowska, Stig E. Bojesen, Jo Perkins, Christi J. van Asperen, Simon S. Cross, Susan M. Domchek, Alice S. Whittemore, J. Margriet Collée, Trinidad Caldés, Rosemarie Davidson, Judy Garber, Nina Ditsch, Norbert Arnold, Annika Lindblom, Taru A. Muranen, Rodney J. Scott, Hans Ulrich Ulmer, Åke Borg, Qin Wang, V. Arndt, Christoph Engel, Hermann Brenner, Esther M. John, Rita K. Schmutzler, Julian Peto, Jan Lubinski, Børge G. Nordestgaard, Diana Torres, Barbara Burwinkel, Natalia Bogdanova, Caroline Seynaeve, Steve Ellis, Per Hall, Daniela Zaffaroni, Peter Hillemanns, Yon Ko, Mark E. Robson, Arif B. Ekici, Roger L. Milne, Nadine Tung, Petra Seibold, Marco Montagna, Stephen J. Chanock, Louise Izatt, Andrew K. Godwin, Mervi Grip, Rohini Rau-Murthy, Anna González-Neira, Amanda E. Toland, Anna Marie Mulligan, Noralane M. Lindor, Daniel Barrowdale, Louise A. Brinton, Olivia Fletcher, Anita Bane, Dieter Niederacher, Angela Cox, Maartje J. Hooning, Barbara Pasini, Manjeet K. Bolla, Carl Blomqvist, Ros Eeles, Graham G. Giles, and Javier Benitez
Subjects: Oncology, Pathology, Cancer Research, endocrine system diseases, Receptor, ErbB-2, Genes, BRCA2, Genes, BRCA1, Triple Negative Breast Neoplasms, Tumor Status, ErbB-2, Medizinische Fakultät, Receptors, 10. No inequality, skin and connective tissue diseases, Progesterone, Medicine(all), Likelihood Functions, Age Factors, Middle Aged, Adult, Aged, Breast Neoplasms, Carcinoma, Female, Humans, Mutation, Neoplasm Grading, Neoplasm Staging, Receptors, Estrogen, Receptors, Progesterone, 3. Good health, Mutation (genetic algorithm), Receptor, Research Article, medicine.medical_specialty, Breast cancer, Germline mutation, Internal medicine, medicine, Clinical significance, ddc:610, business.industry, Cancer, medicine.disease, BRCA1, Estrogen, BRCA2, BRCA2 Mutation Carrier, Genes, Mutation testing, business
Abstract: Introduction The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach. Results ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)). Conclusions These results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management. Electronic supplementary material The online version of this article (doi:10.1186/s13058-014-0474-y) contains supplementary material, which is available to authorized users.
Published: 2014
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15. An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients

Author: de Elisabeth G. E. Vries, Femke E. Froklage, J G Schrama, M. de Bruin, Michael Hauptmann, M.J. van de Vijver, Esther H. Lips, Sjoerd Rodenhuis, Marieke A. Vollebergh, Sten Cornelissen, Jelle Wesseling, Marjanka K. Schmidt, M. J. Holtkamp, Petra M. Nederlof, Sabine C. Linn, H. van Tinteren, E. H. van Beers, L. F. A. Wessels, Cancer Center Amsterdam, Pathology, Other departments, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: Oncology, endocrine system diseases, Receptor, ErbB-2, OVARIAN-TUMORS, Carboplatin, Immunoenzyme Techniques, chemistry.chemical_compound, Antineoplastic Combined Chemotherapy Protocols, platinum salt, skin and connective tissue diseases, Promoter Regions, Genetic, In Situ Hybridization, Fluorescence, GENE-EXPRESSION, Comparative Genomic Hybridization, Predictive marker, BRCA1 Protein, Hematology, Chemotherapy regimen, Survival Rate, Treatment Outcome, Receptors, Estrogen, CARCINOMAS, PHASE-II, TRIAL, Female, Breast disease, Fluorouracil, Receptors, Progesterone, predictive marker, Epirubicin, medicine.drug, Adult, medicine.medical_specialty, Anthracycline, Breast Neoplasms, MUTATION CARRIERS, Breast cancer, array comparative genomic hybridisation, Internal medicine, Breast Cancer, medicine, Humans, Cyclophosphamide, business.industry, Cancer, Original Articles, DNA Methylation, medicine.disease, BRCA1, ESTROGEN-RECEPTOR, chemistry, Carcinoma, Basal Cell, Mutation, Cancer research, business, BRCA1 MUTATIONS, Thiotepa, high-dose chemotherapy, Follow-Up Studies
Abstract: Background: Breast cancer cells deficient for BRCA1 are hypersensitive to agents inducing DNA double-strand breaks (DSB), such as bifunctional alkylators and platinum agents. Earlier, we had developed a comparative genomic hybridisation (CGH) classifier based on BRCA1-mutated breast cancers. We hypothesised that this BRCA1-likeCGH classifier could also detect loss of function of BRCA1 due to other causes besides mutations and, consequently, might predict sensitivity to DSB-inducing agents. Patients and methods: We evaluated this classifier in stage III breast cancer patients, who had been randomly assigned between adjuvant high-dose platinum-based (HD-PB) chemotherapy, a DSB-inducing regimen, and conventional anthracycline-based chemotherapy. Additionally, we assessed BRCA1 loss through mutation or promoter methylation and immunohistochemical basal-like status in the triple-negative subgroup (TN subgroup). Results: We observed greater benefit from HD-PB chemotherapy versus conventional chemotherapy among patients with BRCA1-likeCGH tumours [41/230 = 18%, multivariate hazard ratio (HR) = 0.12, 95% confidence interval (CI) 0.04–0.43] compared with patients with non-BRCA1-likeCGH tumours (189/230 = 82%, HR = 0.78, 95% CI 0.50–1.20), with a significant difference (test for interaction P = 0.006). Similar results were obtained for overall survival (P interaction = 0.04) and when analyses were restricted to the TN subgroup. Sixty-three percent (20/32) of assessable BRCA1-likeCGH tumours harboured either a BRCA1 mutation (n = 8) or BRCA1 methylation (n = 12). Conclusion: BRCA1 loss as assessed by CGH analysis can identify patients with substantially improved outcome after adjuvant DSB-inducing chemotherapy when compared with standard anthracycline-based chemotherapy in our series.
Published: 2010

16. Abstract 2793: Not HOXB13 p.G84E, but p.R217C appears to be associated with increased breast cancer risk in the Dutch population

Author: John W.M. Martens, Marjanka K. Schmidt, Sten Cornelissen, Wendy J. C. Prager-van der Smissen, Margriet Collée, Antoinette Hollestelle, Jingjing Liu, and Ans W.M. van den Ouweland
Subjects: Oncology, Gynecology, Cancer Research, medicine.medical_specialty, education.field_of_study, business.industry, Population, Cancer, Gene mutation, medicine.disease, Prostate cancer, Breast cancer, Germline mutation, Internal medicine, medicine, Missense mutation, education, business, Allele frequency
Abstract: Recently, the germline mutation G84E in HOXB13 was shown to be associated with an increased risk for prostate cancer. In breast cancer, HOXB13 has been found to be overexpressed. Moreover, high expression of HOXB13 has been shown to mediate poor response to tamoxifen therapy by suppressing estrogen receptor α and inducing IL-6 expression. Based on these observations, the HOXB13 G84E mutation might also be associated with breast cancer risk. So far, the association between HOXB13 G84E and breast cancer risk has been investigated in three different studies and contradictory results were obtained. The goal of this study is to detect if HOXB13 gene mutations in general associate with breast cancer risk. To this end, we sequenced the whole HOXB13 coding region to find mutations in 1250 non-BRCA1&2 familial breast cancer cases and 800 controls. In total, thirteen variants were detected, including seven missense mutations. The G84E mutation was identified in 4 of 1215 cases (0.33%) and 6 of 759 controls (0.79%). Interestingly, we detected another mutation G217C in 6 of 1206 cases (0.50%) and 1 of 765 controls (0.13%). The other five missense mutations were only found once. Because both the HOXB13 G84E and R217C mutations were predicted to be probably damaging, we further evaluated if these two mutations were associated with breast cancer risk. Therefore we expanded our case-control study to include a total of 4520 non-BRCA1&2 familial breast cancer cases and 3127 controls by Taqman genotyping. Our preliminary results show that the HOXB13 G84E mutation was found in 22 of 4449 cases (0.49%) and 23 of 3089 controls (0.74%). The carrier allele frequency was higher in controls than in cases, but not significantly different (OR = 0.66, 95% CI = 0.37-1.19, p = 0.17). Our results indicate that the HOXB13 G84E mutation is not associated with breast cancer risk. The HOXB13 R217C mutation was identified in 15 of 4478 cases (0.33%) and 3 of 3077 controls (0.10%). This difference was borderline significant (OR = 3.44, 95% CI = 1.00-11.91, p = 0.052) most likely due to low population frequency in combination with a relatively small sample size. The HOXB13 R217C mutation could thus be a novel moderate-risk breast cancer susceptibility allele, however a larger study is needed to confirm these results. In conclusion, the R217C mutation rather than the G84E mutation in HOXB13 appears to be associated with breast cancer risk. Citation Format: Jingjing Liu, Wendy JC Prager-van der Smissen, Sten Cornelissen, Margriet J. Collee, Ans W.M. van den Ouweland, Marjanka K. Schmidt, John W.M. Martens, Antoinette Hollestelle. Not HOXB13 p.G84E, but p.R217C appears to be associated with increased breast cancer risk in the Dutch population. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2793. doi:10.1158/1538-7445.AM2015-2793
Published: 2015
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17. Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with prognosis of estrogen receptor-negative breast cancer after chemotherapy

Author: Chen-Yang Shen, Keun-Young Yoo, Kazuo Tajima, Georgia Chenevix-Trench, Qin Wang, William J. Tapper, Kristiina Aittomäki, Douglas F. Easton, Anne Lise Børresen-Dale, Ann Smeets, Hidemi Ito, Heli Nevanlinna, Kamila Czene, Sabine C. Linn, Soo Hwang Teo, Tom Maishman, Ursula Eilber, Robert Luben, Jolanta Lissowska, Cheng Har Yip, Keitaro Matsuo, Sue K. Park, Sandrine Tchatchou, Lothar Haeberle, Anja Rudolph, Sajjad Rafiq, Ellen L. Goode, Nur Aishah Taib, Arto Mannermaa, Keith Humphreys, Sabine Behrens, Silje Nord, Javier Benitez, Alison M. Dunning, Irene L. Andrulis, Jaana M. Hartikainen, Sandra Alexandra J van den Broek, Joe Dennis, Gord Glendon, Taru A. Muranen, Arif B. Ekici, Veli-Matti Kosma, Madeleine M.A. Tilanus-Linthorst, Annika Lindblom, Emily Hallberg, Vessela N. Kristensen, Diana Eccles, Maartje J. Hooning, Sten Cornelissen, Stephen J. Chanock, Paul P.D. Pharoah, Diana Torres, Carolien H.M. van Deurzen, Jingmei Li, Celine M. Vachon, Pei-Ei Wu, Jenny Chang-Claude, Fergus J. Couch, Hans-Ulrich Ulmer, Jieping Lei, Sigrid Hatse, Vesa Kataja, Ute Hamann, Sara Margolin, Daehee Kang, Marjanka K. Schmidt, Hans Wildiers, Lara Sucheston, Janet E. Olson, Mitul Shah, Matthias W. Beckmann, Manjeet K. Bolla, Ji Yeob Choi, Per Hall, Carl Blomqvist, Thomas Rüdiger, Gwo Fuang Ho, Jonine D. Figueroa, Julia A. Knight, Petra Seibold, Chia-Ni Hsiung, Ming-Feng Hou, Hiroji Iwata, Diether Lambrechts, Kelly-Anne Phillips, Grethe I. Grenaker Alnæs, Peter A. Fasching, Montserrat Garcia-Closas, Kirsten B. Moysich, Agnes Jager, Pharoah, Paul [0000-0001-8494-732X], Dennis, Joe [0000-0003-4591-1214], Wang, Jean [0000-0002-9139-0627], Luben, Robert [0000-0002-5088-6343], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Medical Oncology, Clinical Genetics, Pathology, and Surgery
Subjects: Oncology, medicine.medical_treatment, Estrogen receptor, 32 Biomedical and Clinical Sciences, Genome-wide association study, Kaplan-Meier Estimate, 0302 clinical medicine, Medizinische Fakultät, Surgical oncology, Antineoplastic Combined Chemotherapy Protocols, 2.1 Biological and endogenous factors, Prospective cohort study, health care economics and organizations, Cancer, 2 Aetiology, Medicine(all), 0303 health sciences, Interleukin-12 Subunit p40, Hazard ratio, Genomics, Middle Aged, Prognosis, Tumor Burden, 3. Good health, 3204 Immunology, Treatment Outcome, Receptors, Estrogen, 030220 oncology & carcinogenesis, Female, 4.2 Evaluation of markers and technologies, Signal Transduction, Research Article, Adult, medicine.medical_specialty, Breast Neoplasms, Single-nucleotide polymorphism, Protein Serine-Threonine Kinases, Polymorphism, Single Nucleotide, Immunomodulation, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, Breast Cancer, Genetics, Biomarkers, Tumor, medicine, Humans, ddc:610, Neoplasm Staging, 030304 developmental biology, Chemotherapy, business.industry, Receptor, Transforming Growth Factor-beta Type II, 3211 Oncology and Carcinogenesis, medicine.disease, Cancer research, Neoplasm Grading, 4 Detection, screening and diagnosis, business, Receptors, Transforming Growth Factor beta
Abstract: Introduction Tumor lymphocyte infiltration is associated with clinical response to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify variants in immunosuppressive pathway genes associated with prognosis after adjuvant chemotherapy for ER-negative patients, we studied stage I-III invasive breast cancer patients of European ancestry, including 9,334 ER-positive (3,151 treated with chemotherapy) and 2,334 ER-negative patients (1,499 treated with chemotherapy). Methods We pooled data from sixteen studies from the Breast Cancer Association Consortium (BCAC), and employed two independent studies for replications. Overall 3,610 single nucleotide polymorphisms (SNPs) in 133 genes were genotyped as part of the Collaborative Oncological Gene-environment Study, in which phenotype and clinical data were collected and harmonized. Multivariable Cox proportional hazard regression was used to assess genetic associations with overall survival (OS) and breast cancer-specific survival (BCSS). Heterogeneity according to chemotherapy or ER status was evaluated with the log-likelihood ratio test. Results Three independent SNPs in TGFBR2 and IL12B were associated with OS (P C) (per allele hazard ratio (HR) 1.54 (95% confidence interval (CI) 1.22 to 1.95), P = 3.08 × 10−4) was not found in ER-negative patients without chemotherapy or ER-positive patients with chemotherapy (P for interaction A) with poorer OS (HR 1.50 (95% CI 1.21 to 1.86), P = 1.81 × 10−4), and rs2853694 (A > C) with improved OS (HR 0.73 (95% CI 0.61 to 0.87), P = 3.67 × 10−4). Similar associations were observed with BCSS. Association with TGFBR2 rs1367610 but not IL12B variants replicated using BCAC Asian samples and the independent Prospective Study of Outcomes in Sporadic versus Hereditary Breast Cancer Study and yielded a combined HR of 1.57 ((95% CI 1.28 to 1.94), P = 2.05 × 10−5) without study heterogeneity. Conclusions TGFBR2 variants may have prognostic and predictive value in ER-negative breast cancer patients treated with adjuvant chemotherapy. Our findings provide further insights into the development of immunotherapeutic targets for ER-negative breast cancer.
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17 results on '"Sten Cornelissen"'

1. Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma

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

3. P01.15 Personalized combination of neoadjuvant domatinostat, nivolumab (NIVO) and ipilimumab (IPI) in macroscopic stage III melanoma patients stratified according to interferon-gamma (IFN-gamma) signature – the DONIMI study

4. LBA39 Personalized combination of neoadjuvant domatinostat, nivolumab (NIVO) and ipilimumab (IPI) in stage IIIB-D melanoma patients (pts) stratified according to the interferon-gamma signature (IFN-γ sign): The DONIMI study

5. A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer

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7. Reproductive profiles and risk of breast cancer subtypes: a multi-center case-only study

8. Association analysis identifies 65 new breast cancer risk loci

9. Evaluation of the EGFR polymorphism R497K in two cohorts of neoadjuvantly treated breast cancer patients

10. Age- and Tumor Subtype Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers

11. 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium

12. 11q13 is a susceptibility locus for hormone receptor positive breast cancer

13. Impact of Age at Primary Breast Cancer on Contralateral Breast Cancer Risk in BRCA1/2 Mutation Carriers

14. Refined histopathological predictors of BRCA1 and BRCA2mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

15. An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients

16. Abstract 2793: Not HOXB13 p.G84E, but p.R217C appears to be associated with increased breast cancer risk in the Dutch population

17. Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with prognosis of estrogen receptor-negative breast cancer after chemotherapy

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