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. 2012 Jan;21(1):134-47.
doi: 10.1158/1055-9965.EPI-11-0775. Epub 2011 Dec 5.

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

Nasim Mavaddat  1 , Daniel Barrowdale, Irene L Andrulis, Susan M Domchek, Diana Eccles, Heli Nevanlinna, Susan J Ramus, Amanda Spurdle, Mark Robson, Mark Sherman, Anna Marie Mulligan, Fergus J Couch, Christoph Engel, Lesley McGuffog, Sue Healey, Olga M Sinilnikova, Melissa C Southey, Mary Beth Terry, David Goldgar, Frances O'Malley, Esther M John, Ramunas Janavicius, Laima Tihomirova, Thomas V O Hansen, Finn C Nielsen, Ana Osorio, Alexandra Stavropoulou, Javier Benítez, Siranoush Manoukian, Bernard Peissel, Monica Barile, Sara Volorio, Barbara Pasini, Riccardo Dolcetti, Anna Laura Putignano, Laura Ottini, Paolo Radice, Ute Hamann, Muhammad U Rashid, Frans B Hogervorst, Mieke Kriege, Rob B van der Luijt; HEBON; Susan Peock, Debra Frost, D Gareth Evans, Carole Brewer, Lisa Walker, Mark T Rogers, Lucy E Side, Catherine Houghton; EMBRACE; 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; GEMO Study Collaborators; Claudine Isaacs, Beth N Peshkin, Trinidad Caldes, Miguel de la Hoya, Carmen Cañadas, Tuomas Heikkinen, Päivi Heikkilä, Kristiina Aittomäki, Ignacio Blanco, Conxi Lazaro, Joan Brunet, Bjarni A Agnarsson, Adalgeir Arason, Rosa B Barkardottir, Martine Dumont, Jacques Simard, Marco Montagna, Simona Agata, Emma D'Andrea, Max Yan, Stephen Fox; kConFab Investigators; Timothy R Rebbeck, Wendy Rubinstein, Nadine Tung, Judy E Garber, Xianshu Wang, Zachary Fredericksen, Vernon S Pankratz, Noralane M Lindor, Csilla Szabo, Kenneth Offit, Rita Sakr, Mia M Gaudet, Christian F Singer, Muy-Kheng Tea, Christine Rappaport, Phuong L Mai, Mark H Greene, Anna Sokolenko, Evgeny Imyanitov, Amanda Ewart Toland, Leigha Senter, Kevin Sweet, Mads Thomassen, Anne-Marie Gerdes, Torben Kruse, Maria Caligo, Paolo Aretini, Johanna Rantala, Anna von Wachenfeld, Karin Henriksson; SWE-BRCA Collaborators; Linda Steele, Susan L Neuhausen, Robert Nussbaum, Mary Beattie, Kunle Odunsi, Lara Sucheston, Simon A Gayther, Kate Nathanson, Jenny Gross, Christine Walsh, Beth Karlan, Georgia Chenevix-Trench, Douglas F Easton, Antonis C Antoniou; Consortium of Investigators of Modifiers of BRCA1/2
Collaborators, Affiliations

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

Nasim Mavaddat et al. Cancer Epidemiol Biomarkers Prev. 2012 Jan.

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.

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Figures

Figure 1
Figure 1. Age specific proportions of Grade 1, 2 and 3 breast tumors arising in BRCA1 and BRCA2 mutation carriers
Age specific proportions of Grade 1, Grade 2, and Grade 3 tumors among (A) BRCA1 and (B) BRCA2 mutation carriers. Error bars represent robust confidence intervals associated with each proportion.
Figure 2
Figure 2. Age specific proportions of pathological subtypes of breast tumors arising in BRCA1 and BRCA2 mutation carriers
Age specific proportions of (A) Receptor-negative (ER, PR) (B) HER2-negative, and (C) triple negative tumors arising in BRCA1 mutation carriers, and of (D) Receptor-negative (ER, PR) (E) HER2-negative, and (F) triple negative tumors arising in BRCA2 mutation carriers. ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2. Error bars represent robust confidence intervals associated with each proportion.
Figure 3
Figure 3. Distribution of Grade within ER-positive and ER-negative BRCA1 and BRCA2 mutation carriers
Age specific proportions of Grade 1, Grade 2, and Grade 3 (A) ER-negative, and (C) ER-positive breast tumors arising in BRCA1 mutation carriers, and (B) ER-negative, and (D) ER-positive breast tumors arising in BRCA2 mutation carriers. ER, estrogen receptor
See this image and copyright information in PMC

References

    1. Armes JE, Egan AJ, Southey MC, Dite GS, McCredie MR, Giles GG, et al. The histologic phenotypes of breast carcinoma occurring before age 40 years in women with and without BRCA1 or BRCA2 germline mutations: a population-based study. Cancer. 1998;83:2335–45. - PubMed
    1. Lakhani SR, Jacquemier J, Sloane JP, Gusterson BA, Anderson TJ, Van De Vijver MJ, et al. Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst. 1998;90:1138–45. - PubMed
    1. Southey MC, Ramus SJ, Dowty JG, Smith LD, Tesoriero AA, Wong EE, et al. Morphological predictors of BRCA1 germline mutations in young women with breast cancer. Br J Cancer. 2011;104:903–9. - PMC - PubMed
    1. Eisinger F, Jacquemier J, Charpin C, Stoppa-Lyonnet D, Bressac-de PB, Peyrat JP, et al. Mutations at BRCA1: the medullary breast carcinoma revisited. Cancer Res. 1998;58:1588–92. - PubMed
    1. Iau PT, Marafie M, Ali A, Sng JH, Macmillan RD, Pinder S, et al. Are medullary breast cancers an indication for BRCA1 mutation screening? A mutation analysis of 42 cases of medullary breast cancer. Breast Cancer Res Treat. 2004;85:81–8. - PubMed

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