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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).

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Authors
Mavaddat, Nasim
Barrowdale, Daniel
Andrulis, Irene L
Domchek, Susan M
Eccles, Diana
Nevanlinna, Heli
Ramus, Susan J
Spurdle, Amanda
Robson, Mark
Sherman, Mark
Mulligan, Anna Marie
Couch, Fergus J
Engel, Christoph
McGuffog, Lesley
Healey, Sue
Sinilnikova, Olga M
Southey, Melissa C
Terry, Mary Beth
Goldgar, David
O'Malley, Frances
John, Esther M
Janavicius, Ramunas
Tihomirova, Laima
Hansen, Thomas V O
Nielsen, Finn C
Osorio, Ana
Stavropoulou, Alexandra
Benítez, Javier
Manoukian, Siranoush
Peissel, Bernard
Barile, Monica
Volorio, Sara
Pasini, Barbara
Dolcetti, Riccardo
Putignano, Anna Laura
Ottini, Laura
Radice, Paolo
Hamann, Ute
Rashid, Muhammad U
Hogervorst, Frans B
Kriege, Mieke
van der Luijt, Rob B
Peock, Susan
Frost, Debra
Evans, D Gareth
Brewer, Carole
Walker, Lisa
Rogers, Mark T
Side, Lucy E
Houghton, Catherine
Weaver, JoEllen
Godwin, Andrew K
Schmutzler, Rita K
Wappenschmidt, Barbara
Meindl, Alfons
Kast, Karin
Arnold, Norbert
Niederacher, Dieter
Sutter, Christian
Deissler, Helmut
Gadzicki, Doroteha
Preisler-Adams, Sabine
Varon-Mateeva, Raymonda
Schönbuchner, Ines
Gevensleben, Heidrun
Stoppa-Lyonnet, Dominique
Belotti, Muriel
Barjhoux, Laure
Isaacs, Claudine
Peshkin, Beth N
Caldes, Trinidad
de la Hoya, Miguel
Cañadas, Carmen
Heikkinen, Tuomas
Heikkilä, Päivi
Aittomäki, Kristiina
Blanco, Ignacio
Lazaro, Conxi
Brunet, Joan
Agnarsson, Bjarni A
Arason, Adalgeir
Barkardottir, Rosa B
Dumont, Martine
Simard, Jacques
Montagna, Marco
Agata, Simona
D'Andrea, Emma
Yan, Max
Fox, Stephen
Rebbeck, Timothy R
Rubinstein, Wendy
Tung, Nadine
Garber, Judy E
Wang, Xianshu
Fredericksen, Zachary
Pankratz, Vernon S
Lindor, Noralane M
Szabo, Csilla
Offit, Kenneth
Sakr, Rita
Gaudet, Mia M
Singer, Christian F
Tea, Muy-Kheng
Rappaport, Christine
Mai, Phuong L
Greene, Mark H
Sokolenko, Anna
Imyanitov, Evgeny
Toland, Amanda Ewart
Senter, Leigha
Sweet, Kevin
Thomassen, Mads
Gerdes, Anne-Marie
Kruse, Torben
Caligo, Maria
Aretini, Paolo
Rantala, Johanna
von Wachenfeld, Anna
Henriksson, Karin
Steele, Linda
Neuhausen, Susan L
Nussbaum, Robert
Beattie, Mary
Odunsi, Kunle
Sucheston, Lara
Gayther, Simon A
Nathanson, Kate
Gross, Jenny
Walsh, Christine
Karlan, Beth
Chenevix-Trench, Georgia
Easton, Douglas F
Antoniou, Antonis C
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Issue Date
2012-01

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Citation
Cancer Epidemiol. Biomarkers Prev. 2012, 21(1):134-47
Abstract
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. 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. 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.
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To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.
Additional Links
http://dx.doi.org/10.1158/1055-9965.EPI-11-0775
http://cebp.aacrjournals.org/content/21/1/134.full.pdf+html
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272407/
Rights
Archived with thanks to Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ae974a485f413a2113503eed53cd6c53
10.1158/1055-9965.EPI-11-0775
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