RT Journal Article SR Electronic T1 Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) JF Cancer Epidemiology Biomarkers & Prevention JO Cancer Epidemiol Biomarkers Prev FD American Association for Cancer Research SP 134 OP 147 DO 10.1158/1055-9965.EPI-11-0775 VO 21 IS 1 A1 Mavaddat, Nasim A1 Barrowdale, Daniel A1 Andrulis, Irene L. A1 Domchek, Susan M. A1 Eccles, Diana A1 Nevanlinna, Heli A1 Ramus, Susan J. A1 Spurdle, Amanda A1 Robson, Mark A1 Sherman, Mark A1 Mulligan, Anna Marie A1 Couch, Fergus J. A1 Engel, Christoph A1 McGuffog, Lesley A1 Healey, Sue A1 Sinilnikova, Olga M. A1 Southey, Melissa C. A1 Terry, Mary Beth A1 Goldgar, David A1 O'Malley, Frances A1 John, Esther M. A1 Janavicius, Ramunas A1 Tihomirova, Laima A1 Hansen, Thomas V. O. A1 Nielsen, Finn C. A1 Osorio, Ana A1 Stavropoulou, Alexandra A1 Benítez, Javier A1 Manoukian, Siranoush A1 Peissel, Bernard A1 Barile, Monica A1 Volorio, Sara A1 Pasini, Barbara A1 Dolcetti, Riccardo A1 Putignano, Anna Laura A1 Ottini, Laura A1 Radice, Paolo A1 Hamann, Ute A1 Rashid, Muhammad U. A1 Hogervorst, Frans B. A1 Kriege, Mieke A1 van der Luijt, Rob B. A1 Peock, Susan A1 Frost, Debra A1 Evans, D. Gareth A1 Brewer, Carole A1 Walker, Lisa A1 Rogers, Mark T. A1 Side, Lucy E. A1 Houghton, Catherine A1 Weaver, JoEllen A1 Godwin, Andrew K. A1 Schmutzler, Rita K. A1 Wappenschmidt, Barbara A1 Meindl, Alfons A1 Kast, Karin A1 Arnold, Norbert A1 Niederacher, Dieter A1 Sutter, Christian A1 Deissler, Helmut A1 Gadzicki, Doroteha A1 Preisler-Adams, Sabine A1 Varon-Mateeva, Raymonda A1 Schönbuchner, Ines A1 Gevensleben, Heidrun A1 Stoppa-Lyonnet, Dominique A1 Belotti, Muriel A1 Barjhoux, Laure A1 Isaacs, Claudine A1 Peshkin, Beth N. A1 Caldes, Trinidad A1 de la Hoya, Miguel A1 Cañadas, Carmen A1 Heikkinen, Tuomas A1 Heikkilä, Päivi A1 Aittomäki, Kristiina A1 Blanco, Ignacio A1 Lazaro, Conxi A1 Brunet, Joan A1 Agnarsson, Bjarni A. A1 Arason, Adalgeir A1 Barkardottir, Rosa B. A1 Dumont, Martine A1 Simard, Jacques A1 Montagna, Marco A1 Agata, Simona A1 D'Andrea, Emma A1 Yan, Max A1 Fox, Stephen A1 Rebbeck, Timothy R. A1 Rubinstein, Wendy A1 Tung, Nadine A1 Garber, Judy E. A1 Wang, Xianshu A1 Fredericksen, Zachary A1 Pankratz, Vernon S. A1 Lindor, Noralane M. A1 Szabo, Csilla A1 Offit, Kenneth A1 Sakr, Rita A1 Gaudet, Mia M. A1 Singer, Christian F. A1 Tea, Muy-Kheng A1 Rappaport, Christine A1 Mai, Phuong L. A1 Greene, Mark H. A1 Sokolenko, Anna A1 Imyanitov, Evgeny A1 Toland, Amanda Ewart A1 Senter, Leigha A1 Sweet, Kevin A1 Thomassen, Mads A1 Gerdes, Anne-Marie A1 Kruse, Torben A1 Caligo, Maria A1 Aretini, Paolo A1 Rantala, Johanna A1 von Wachenfeld, Anna A1 Henriksson, Karin A1 Steele, Linda A1 Neuhausen, Susan L. A1 Nussbaum, Robert A1 Beattie, Mary A1 Odunsi, Kunle A1 Sucheston, Lara A1 Gayther, Simon A. A1 Nathanson, Kate A1 Gross, Jenny A1 Walsh, Christine A1 Karlan, Beth A1 Chenevix-Trench, Georgia A1 Easton, Douglas F. A1 Antoniou, Antonis C. YR 2012 UL http://cebp.aacrjournals.org/content/21/1/134.abstract AB 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.