Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study

Background Women with a mutation in BRCA1 or BRCA2 have a high risk of deve loping breast cancer and of contralateral cancer after the initial diagnosi s of breast cancer. Tamoxifen protects against contralateral breast cancer in the general population, but whether it protects against contralateral br east cancer in BRCA1 or BRCA2 mutation carriers is not known. Methods We compared 209 women with bilateral breast cancer and BRCA1 or BRC A2 mutation (bilateral-disease cases), with 384 women with unilateral disea se and BRCA1 or BRCA2 mutation (controls) in a matched case-control study. Age and age at diagnosis of breast cancer (range 24-74 years) were much the same in bilateral-disease cases and controls, and both groups had been fol lowed up for the same time for a second primary breast cancer. History of t amoxifen use for first breast cancer was obtained by interview, or by self- administered questionnaire. Findings The multivariate adds ratio for contralateral breast cancer associ ated with tamoxifen;use was 0.50 (95% CI 0.28-0.89). Tamoxifen protected ag ainst contralateral breast cancer for carriers of BRCA1 mutations (odds rat io 0.38, 95% CI 0.19-0.74) and for those with BRCA2 mutations (0.63, 0.20-1 .50). In women who used tamoxifen for 2-4 years, the risk of contralateral breast cancer was reduced by 75%. A reduction in risk of contralateral canc er was also seen with oophorectomy (0.42, 0.22-0.83) and with chemotherapy (0.40, 0.26-0.60). Interpretation Tamoxifen use reduces the risk of contralateral breast cance r in women with pathogenic mutations in the BRCA1 or BRCA2 gene. The protec tive effect of tamoxifen seems independent of that of oophorectomy.