Oral contraceptive use and breast cancer risk: retrospective and prospective analyses from a BRCA1 and BRCA2 mutation carrier cohort study

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 BC risk associations were estimated from OCP data on 6,030 BRCA1 and 3,809 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 from prospective analyses (Hazard Ratio (HR) 1.08;95% Confidence Interval (CI) 0.75-1.56), but from the left-truncated and full-cohort retrospective analyses risks were increased by 26% (95%CI 6%-51%) and 39% (95%CI 23%-58%), respectively. For BRCA2 mutation carriers, OCP use was associated with BC risk from prospective analyses (HR 1.75;95%CI 1.03-2.97), but retrospective analyses were inconsistent (left-truncated: HR 1.06;95%CI 0.85-1.33; full-cohort: HR 1.52;95%CI 1.28-1.81). There was evidence of increasing risk with duration of use, especially before first full-term pregnancy (BRCA1: both retrospective analyses, p<0.001 and p=0.001, respectively; BRCA2: full-retrospective analysis, p=0.002). 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 age 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 uncertain safety of OCP use for BRCA1/2 mutation carriers, indications other than contraception should be avoided and non-hormonal contraceptive methods discussed.