Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study.

Lieske H Schrijver ,Brita Arver,Dominique Leroux,Debra Frost,Rosemarie Davidson,Valérie Bonadona,Steve Ellis,Catherine Noguès,Daniel Barrowdale,Pascaline Berthet,Anna Jakubowska,Emmanuelle Mouret-Fourme,Anita Bane,Marie-José Roos-Blom,Håkan Olsson,Mary Beth Terry,Anne-Marie Gerdes,Julian Adlard,Karin Kast,Jacques Simard,Ros Eeles,Ana Osorio,Christoph Engel,Nadine Andrieu,Louise Izatt,Lisa Walker,Matti A Rookus ,Esther M John ,Douglas F Easton ,David E Goldgar ,Laurence Vénat-Bouvet ,Genepso Embrace ,Michael Friedlander ,Flora E Van Leeuwen ,Kelly‐Anne Phillips ,Trinidad Caldés ,Encarna B Gómez García ,Yen Y Tan ,Wendy K Chung ,Sue‐Anne Mclachlan ,Edith Oláh ,Lucy Side ,Christi J Van Asperen ,Antonis C Antoniou ,Lenka Foretová ,Thea M Mooij ,Mary Porteous ,John L Hopper ,Theo A.m Van Os ,Christian F Singer ,Roger L Milne ,Mary B Daly ,Marian J.e Mourits ,Melissa C Southey ,Marie Navrátilová ,Saundra S Buys ,D Gareth Evans ,Ibccs

doi:10.1093/jncics/pky023

Abstract

BackgroundFor BRCA1 and BRCA2 mutation carriers, the association between oral contraceptive preparation (OCP) use and breast cancer (BC) risk is still unclear.MethodsBreast camcer risk associations were estimated from OCP data on 6030 BRCA1 and 3809 BRCA2 mutation carriers using age-dependent Cox regression, stratified by study and birth cohort. Prospective, left-truncated retrospective and full-cohort retrospective analyses were performed.ResultsFor BRCA1 mutation carriers, OCP use was not associated with BC risk in prospective analyses (hazard ratio [HR] = 1.08, 95% confidence interval [CI] = 0.75 to 1.56), but in the left-truncated and full-cohort retrospective analyses, risks were increased by 26% (95% CI = 6% to 51%) and 39% (95% CI = 23% to 58%), respectively. For BRCA2 mutation carriers, OCP use was associated with BC risk in prospective analyses (HR = 1.75, 95% CI = 1.03 to 2.97), but retrospective analyses were inconsistent (left-truncated: HR = 1.06, 95% CI = 0.85 to 1.33; full cohort: HR = 1.52, 95% CI = 1.28 to 1.81). There was evidence of increasing risk with duration of use, especially before the first full-term pregnancy (BRCA1: both retrospective analyses, P < .001 and P = .001, respectively; BRCA2: full retrospective analysis, P = .002).ConclusionsProspective analyses did not show that past use of OCP is associated with an increased BC risk for BRCA1 mutation carriers in young middle-aged women (40–50 years). For BRCA2 mutation carriers, a causal association is also not likely at those ages. Findings between retrospective and prospective analyses were inconsistent and could be due to survival bias or a true association for younger women who were underrepresented in the prospective cohort. Given the uncertain safety of long-term OCP use for BRCA1/2 mutation carriers, indications other than contraception should be avoided and nonhormonal contraceptive methods should be discussed.

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