Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers: A combined analysis from the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab), the International BRCA1 and BRCA2Carrier Cohort Study (IBCCS), and the Breast Cancer Family Registry (BCFR).

Abstract

1500 Background: Whether tamoxifen is effective as a breast cancer (BC) prevention strategy for BRCA1 and BRCA2 mutation carriers is uncertain. Methods: Female BRCA1 and BRCA2 mutation carriers, with a personal history of BC since 1970, enrolled in any of the BC family studies, kConFab, IBCCS, or BCFR, were eligible. Those with another invasive cancer or tamoxifen use prior to their first BC diagnosis, or with bilateral disease at first BC diagnosis, were excluded. Data were self-reported at entry into the cohort and at follow-up. Hazard ratios (HRs) for development of contralateral BC associated with tamoxifen use after first BC diagnosis were estimated using Cox proportional hazards, modeling time from diagnosis of first primary BC, adjusting for year of birth (continuous), age at diagnosis (continuous), country and bilateral oophorectomy (yes/no, time-varying) and censoring at contralateral mastectomy, death or loss to follow-up. Results: Of 1642 BRCA1 and 919 BRCA2 mutation carriers, 374 (23%) and 444 (48%), respectively, took tamoxifen after their first BC diagnosis. During 21,344 person-years of follow-up, 596 contralateral BCs were observed. Overall, the adjusted HR estimates were 0.31 (95% CI: 0.22-0.45) and 0.24 (95% CI 0.16-0.35) for BRCA1 and BRCA2 mutation carriers, respectively. After left-truncating the analysis at time of recruitment, the adjusted HR estimates were 0.52 (95% CI: 0.26-1.04) and 0.39 (95% CI: 0.17-0.89) from studying 629 BRCA1 and 412 BRCA2 mutation carriers, respectively, with 4,869 person-years of follow-up. Conclusions: Although biased estimates due to non-random use of tamoxifen cannot be excluded, these results are consistent with tamoxifen reducing BC risk for both BRCA1and BRCA2 mutation carriers.