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Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1 / 2 (CIMBA)

2012; American Association for Cancer Research; Volume: 21; Issue: 1 Linguagem: Inglês

10.1158/1055-9965.epi-11-0775

1538-7755

Nasim Mavaddat, Daniel Barrowdale, Irene L. Andrulis, Susan M. Domchek, Diana Eccles, Heli Nevanlinna, Susan J. Ramus, Amanda B. Spurdle, Mark E. Robson, Mark E. Sherman, Anna Marie Mulligan, Fergus J. Couch, Christoph Engel, Lesley McGuffog, Sue Healey, Olga M. Sinilnikova, Melissa C. Southey, Mary Beth Terry, David E. Goldgar, Frances P. O’Malley, Esther M. John, Ramūnas Janavičius, Laima Tihomirova, Thomas van Overeem Hansen, Finn C. Nielsen, Ana Osório, Alexandra Stavropoulou, Javier Benı́tez, Siranoush Manoukian, Bernard Peissel, Monica Barile, Sara Volorio, Barbara Pasini, Riccardo Dolcetti, Anna Laura Putignano, Laura Ottini, Paolo Radice, Ute Hamann, Muhammad Usman Rashid, Frans B.L. Hogervorst, Mieke Kriege, Rob B. van der Luijt, Susan Peock, Debra Frost, D. Gareth Evans, Carole Brewer, Lisa Walker, Mark T. Rogers, Lucy Side, Catherine Houghton, JoEllen Weaver, Andrew K. Godwin, Rita K. Schmutzler, Barbara Wappenschmidt, Alfons Meindl, Karin Kast, Norbert Arnold, Dieter Niederacher, Christian Sutter, Helmut Deißler, Doroteha Gadzicki, Sabine Preisler‐Adams, Raymonda Varon-Mateeva, Ines Schönbuchner, Heidrun Gevensleben, Dominique Stoppa‐Lyonnet, Muriel Belotti, Laure Barjhoux, Claudine Isaacs, Beth N. Peshkin, Trinidad Caldés, Miguel de la Hoya, Carmen Cañadas, Tuomas Heikkinen, Päivi Heikkilä, Kristiina Aittomäki, Ignacio Blanco, Conxi Lázaro, Joan Brunet, Bjarni A. Agnarsson, Aðalgeir Arason, Rósa B. Barkardóttir, Martine Dumont, Jacques Simard, Marco Montagna, Simona Agata, Emma D’Andrea, Max Yan, Stephen B. Fox, Timothy R. Rebbeck, Wendy S. Rubinstein, Nadine Tung, Judy E. Garber, Xianshu Wang, Zachary Fredericksen, V. Shane Pankratz, Noralane M. Lindor, Csilla I. Szabo, Kenneth Offit, Rita A. Sakr, Mia M. Gaudet, Christian F. Singer, Muy‐Kheng M. Tea, Christine Rappaport, L. Phuong, Mark H. Greene, Anna P. Sokolenko, Evgeny Imyanitov, Amanda E. Toland, Leigha Senter, Kevin Sweet, Mads Thomassen, Anne–Marie Gerdes, Torben A. Kruse, Maria A. Caligo, Paolo Aretini, Johanna Rantala, Anna von Wachenfeld, Karin Henriksson, Linda Steele, Susan L. Neuhausen, Robert L. Nussbaum, Mary Beattie, Kunle Odunsi, Lara Sucheston, Simon A. Gayther, Katherine L. Nathanson, Jenny Gross, Christine Walsh, Beth Y. Karlan, Georgia Chenevix‐Trench, Douglas F. Easton, Antonis C. Antoniou,

Gene expression and cancer classification

Abstract Background: Previously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization. Methods: We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast cancers. Results: There was strong evidence that the proportion of estrogen receptor (ER)-negative breast tumors decreased with age at diagnosis among BRCA1 (P-trend = 1.2 × 10−5), but increased with age at diagnosis among BRCA2, carriers (P-trend = 6.8 × 10−6). The proportion of triple-negative tumors decreased with age at diagnosis in BRCA1 carriers but increased with age at diagnosis of BRCA2 carriers. In both BRCA1 and BRCA2 carriers, ER-negative tumors were of higher histologic grade than ER-positive tumors (grade 3 vs. grade 1; P = 1.2 × 10−13 for BRCA1 and P = 0.001 for BRCA2). ER and progesterone receptor (PR) expression were independently associated with mutation carrier status [ER-positive odds ratio (OR) for BRCA2 = 9.4, 95% CI: 7.0–12.6 and PR-positive OR = 1.7, 95% CI: 1.3–2.3, under joint analysis]. Lobular tumors were more likely to be BRCA2-related (OR for BRCA2 = 3.3, 95% CI: 2.4–4.4; P = 4.4 × 10−14), and medullary tumors BRCA1-related (OR for BRCA2 = 0.25, 95% CI: 0.18–0.35; P = 2.3 × 10−15). ER-status of the first breast cancer was predictive of ER-status of asynchronous contralateral breast cancer (P = 0.0004 for BRCA1; P = 0.002 for BRCA2). There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous: 67%; mucinous: 1%; endometrioid: 12%; clear-cell: 2%). Conclusions/Impact: Pathologic characteristics of BRCA1 and BRCA2 tumors may be useful for improving risk-prediction algorithms and informing clinical strategies for screening and prophylaxis. Cancer Epidemiol Biomarkers Prev; 21(1); 134–47. ©2011 AACR.