Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology ·Vol. 21 ·No. 1 ·2012-04-25

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,

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.

Article Info

Journal

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Abbr.

Cancer Epidemiol Biomarkers Prev

ISSN

1055-9965

Published

2012-04-25

Indexed

2012-01-09

Updated

2016-12-03

Language

English

Country/Region

United States

NLM ID

9200608

External Links

PubMed source View journal details

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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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