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

Lieske H. Schrijver, Hakan Olsson, Kelly-Anne Phillips, Mary Beth Terry, David E. Goldgar, Karin Kast, Christoph Engel, Thea M. Mooij, Julian Adlard, Daniel Barrowdale, Rosemarie Davidson, Ros Eeles, Steve Ellis, D. Gareth Evans, Debra Frost, Louise Izatt, Mary E. Porteous, Lucy E. Side, Lisa Walker, Pascaline BerthetVal Erie Bonadona, Dominique Leroux, Emmanuelle Mouret-Fourme, Laurence Venat-Bouvet, Saundra S. Buys, Melissa C. Southey, Esther M. John, Wendy K. Chung, Mary B. Daly, Anita Bane, Christi J. van Asperen, Encarna B. Gomez Garcia, Marian J. E. Mourits, Marie-Jose Roos-Blom, Michael L. Friedlander, Sue-Anne McLachlan, Christian F. Singer, Lenka Foretova, Anne-Marie Gerdes, Trinidad Caldes, Edith Olah, Anna Jakubowska, Catherine Nogues, Nadine Andrieu, F. E. van Leeuwen, M. K. Schmidt, R. Wijnands, M. G. E. M. Ausems, M. J. Blok, EMBRACE, GENEPSO, Breast Cancer Family Registry (BCFR), HEBON, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab), IBCCS, Matti A. Rookus*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: For BRCA1 and BRCA2 mutation carriers, the association between oral contraceptive preparation (OCP) use and breast cancer (BC) risk is still unclear.

Methods: Breast 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.

Results: For 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).

Conclusions: Prospective 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 non-hormonal contraceptive methods should be discussed.

Original languageEnglish
Article number023
Number of pages14
JournalJNCI Cancer Spectrum
Issue number2
Publication statusPublished - Apr 2018



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