Women with a mutation inBRCA1orBRCA2face a lifetime risk of breast cancer of ˜80%, and following the first diagnosis the10-year risk of contralateral breast cancer is ˜30%. It has been shown that both tamoxifen and oophorectomy prevent contralateral breast cancer, but it is not clear whether there is a benefit in giving tamoxifen to women who have previously undergone an oophorectomy. Furthermore, the relative degree of protection inBRCA1andBRCA2carriers has not been well evaluated. We studied 285 women with bilateral breast cancer and aBRCA1orBRCA2mutation, and 751 control women with unilateral breast cancer and aBRCA1orBRCA2mutation in a matched case-control study. Control women were of similar age and had a similar age of diagnosis of breast cancer and had been followed for as long as the case for a second primary breast cancer. The history of tamoxifen use for treating the first breast cancer was compared between bilateral and unilateral cases. The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0.50 for carriers ofBRCA1mutations (95% CI, 0.30–0.85) and was 0.42 for carriers ofBRCA2mutations (95% CI, 0.17–1.02). The protective effect of tamoxifen was not seen among women who had undergone an oophorectomy (OR= 0.83; 95%CI, 0.24–2.89) but this subgroup was small. In contrast, a strong protective effect of tamoxifen was apparent among women who were premenopausal or who had undergone natural menopause (OR= 0.44; 95% CI, 0.27–0.65).