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

Lieske Schrijver 1 Håkan Olsson 2 Kelly-Anne Phillips 3, 4 Mary Terry 5 David Goldgar 6 Karin Kast 7 Christoph Engel 8, 9 Thea Mooij 1 Julian Adlard 10 Daniel Barrowdale 11 Rosemarie Davidson 12 Ros Eeles 13 Steve Ellis 11 D Evans 14 Debra Frost 11 Louise Izatt 15 Mary Porteous 16 Lucy Side 17 Lisa Walker 18 Pascaline Berthet 19 Valérie Bonadona 20 Dominique Leroux 21, 22 Emmanuelle Mouret-Fourme 23 Laurence Venat-Bouvet 24 Saundra Buys 25 Melissa Southey 26 Esther John 27, 28 Wendy Chung 29 Mary Daly 30 Anita Bane 31, 32 Christi van Asperen 33 Encarna Gómez Garcia 34 Marian Mourits 35 Theo van Os 36 Marie-José Roos-Blom 1 Michael Friedlander 37, 38 Sue-Anne Mclachlan 4, 39 Christian Singer 40 Yen Tan 40 Lenka Foretova 41 Marie Navratilova 41, 42 Anne-Marie Gerdes 43 Trinidad Caldes 44 Jacques Simard 45 Edith Olah 46 Anna Jakubowska 47 Brita Arver 32 Ana Osorio 48 Catherine Noguès 49 Nadine Andrieu 50 Douglas Easton 11 Flora van Leeuwen 1 John Hopper 4 Roger Milne 4, 51 Antonis Antoniou 11 Matti Rookus 1
Abstract : 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 nonhormonal contraceptive methods should be discussed.
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Submitted on : Monday, September 13, 2021 - 2:43:57 PM
Last modification on : Wednesday, November 17, 2021 - 12:31:31 PM

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Lieske Schrijver, Håkan Olsson, Kelly-Anne Phillips, Mary Terry, David Goldgar, et al.. Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study. JNCI Cancer Spectrum, Oxford University Press, 2021, 2 (2), pky023. ⟨10.1093/jncics/pky023⟩. ⟨inserm-03342591⟩

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