Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: Results from the consortium of investigators of modifiers of BRCA1/2 (CIMBA)

N Mavaddat; D Barrowdale; IL Andrulis; SM Domchek; D Eccles; H Nevanlinna; SJ Ramus; A Spurdle; M Robson; M Sherman; AM Mulligan; FJ Couch; C Engel; L McGuffog; S Healey; OM Sinilnikova; MC Southey; MB Terry; D Goldgar; F O'Malley; EM John; R Janavicius; L Tihomirova; TVO Hansen; FC Nielsen; A Osorio; A Stavropoulou; J Benítez; S Manoukian; B Peissel; M Barile; S Volorio; B Pasini; R Dolcetti; AL Putignano; L Ottini; P Radice; U Hamann; MU Rashid; FB Hogervorst; M Kriege; RB Van Der Luijt; S Peock; D Frost; DG Evans; C Brewer; L Walker; MT Rogers; LE Side; C Houghton; JE Weaver; AK Godwin; RK Schmutzler; B Wappenschmidt; A Meindl; K Kast; N Arnold; D Niederacher; C Sutter; H Deissler; D Gadzicki; S Preisler-Adams; R Varon-Mateeva; I Schönbuchner; H Gevensleben; D Stoppa-Lyonnet; M Belotti; L Barjhoux; C Isaacs; BN Peshkin; T Caldes; M De Al Hoya; C Cañadas; T Heikkinen; P Heikkilä; K Aittomäki; I Blanco; C Lazaro; J Brunet; BA Agnarsson; A Arason; RB Barkardottir; M Dumont; J Simard; M Montagna; S Agata; E D'Andrea; M Yan; S Fox; TR Rebbeck; W Rubinstein; N Tung; JE Garber; X Wang; Z Fredericksen; VS Pankratz; NM Lindor; C Szabo; K Offit; R Sakr

Journal article

Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: Results from the consortium of investigators of modifiers of BRCA1/2 (CIMBA)

N Mavaddat, D Barrowdale, IL Andrulis, SM Domchek, D Eccles, H Nevanlinna, SJ Ramus, A Spurdle, M Robson, M Sherman, AM Mulligan, FJ Couch, C Engel, L McGuffog, S Healey, OM Sinilnikova, MC Southey, MB Terry, D Goldgar, F O'Malley Show all

Cancer Epidemiology Biomarkers and Prevention | Published : 2012

DOI: 10.1158/1055-9965.EPI-11-0775

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 BRCA..

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University of Melbourne Researchers

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Riccardo Dolcetti Author

Stephen Fox Author

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Funding Acknowledgements

The author, A.K. Godwin, thanks the support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. A.K. Godwin is the Chancellors Distinguished Chair in Biomedical Sciences-endowed Professor. This work was supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175). NM was funded by a scholarship from the Medical Research Council. ACA is a CR-UK Senior Cancer Research Fellow. DFE is a CR-UK Principal Research Fellow. This work was supported by the National Cancer Institute, NIH, under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Cancer Prevention Institute of California (U01 CA69417), University of Melbourne (U01 CA69638), and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). This work was supported by Cancer Care Ontario and the U.S. National Cancer Institute, NIH, under RFA # CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and principal investigators. Lithuania: This work is financially supported by the Research Council of Lithuania grant LIG-19/2010 to R. Janavicius. Latvia: L. Tihomirova was financially supported by LSC grants 05.0023.04. and 10.0010.08. The authors thank NEYE Foundation for financial support This study was partially supported financially by the Fundacion Mutua Madrilena, Asociacion Espanola Contra el Cancer and the Spanish Ministry of Science and Innovation (FIS PI08 1120). This was funded, in part, by the Basque Foundation for Health Innovation and Research (BIOEF): BIO07/CA/006. The DKFZ study was supported by the DKFZ. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, and NKI2007-3756 and the ZonMW grant 91109024. EMBRACE is financially supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. G. Evans and F. Lalloo are financially supported by an NIHR grant to the Biomedical Research Centre, Manchester, UK. The investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are financially supported by an NIHR grant to the Biomedical Research Centre at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust. R. Eeles, E. Bancroft, and L. D'Mello are also financially supported by a Cancer Research UK grant C5047/A8385. A.K. Godwinwas funded by U01CA69631, 5U01CA113916, and the Eileen Stein Jacoby Fund. GC-HBOC is financially supported by a grant of the German Cancer Aid (grant 109076) the Centre of Molecular Medicine Cologne (CMMC). This study was supported by The Ligue National Contre le Cancer and The Association "Le cancer du sein, parlons-en!" Award. C. Isaacs and B.N. Peshkin are supported by National Cancer Institute Grant (NCI P30 CA51008-12) and by the Fisher Center for Familial Cancer Research. The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The ILUH group was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund. This work was supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and by the Canadian Breast Cancer Research Alliance-grant #019511. This study was supported by "Ministero della Salute" (grant numbers RFPS 2006-5-341353, ACC2/R6.9 and "Progetto Tumori Femminili"). kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia (funded by NHMRC grants 145684, 288704, and 454508). The MAYO study was supported by NIH grants CA116167, CA128978, a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and awards from the Komen Foundation for the Cure and the Breast Cancer Research Foundation. The research of Drs. P. L. Mai and M. H. Greene was supported by the Intramural Research Program of the U.S. National Cancer Institute and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc. This work has been supported by the Russian Federation for Basic Research (grants 10-04-92601, 11-04-00250, 11-04-00227), the Federal Agency for Science and Innovations (contract 02.740.11.0780), and the Commission of the European Communities (grant PITN-GA-2009-238132). This work was supported by the OSU Comprehensive Cancer Center. Caroline Craven and Michelle O'Connor were responsible for patient accrual and data management. M. Caligo was supported by an ITT (Tuscany Institute for Tumors) grant 2010-2012. S. L. Neuhausen was partially supported by NIH CA74415 and the Morris and Horowitz Families Endowed Professorship. The grant funding was obtained from the NIH, NCI Bay Area Breast Cancer SPORE (P50-CA058207), and the Avon Foundation. Support was also provided from the UCSF Helen Diller Family Comprehensive Cancer Center. UKFOCR was supported by a project grant from CRUK to Paul Pharoah. The funding was obtained from Breast Cancer Research Foundation (to K.L. Nathanson); and Cancer Genetics Network and Marjorie Cohen Foundation (to S.M. Domchek). WCRI acknowledges support from the American Cancer Society, SIOP-06-258-01-CCE.