Regarding the Use of Tamoxifen Post-Oophorectomy to Prevent Hereditary Breast Cancer

Metcalfe et al. conducted a historical cohort study on 491 women with a BRCA1 or BRCA2 mutation who were followed for contralateral breast cancer [6]. The combination of tamoxifen and oophorectomy was particularly effective in women under 50; the hazard ratio associated with this combination of therapy was 0.09 (95% CI, 0.01 to 0.68; P = 0.02).In a matched case-control study, Gronwald et al. studied 285 women with bilateral breast cancer and a BRCA1 or BRCA2 mutation, and 751 control women with unilateral breast cancer and a BRCA1 or BRCA2 mutation [7]. The use of tamoxifen 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 of BRCA1 mutations and was 0.42 for carriers of BRCA2 mutations. However, in contrast to Metcalfe's study, the protective effect of tamoxifen was not present among women who had undergone an oophorectomy (OR = 0.83). However, this subgroup was small and the confidence interval was wide (95%CI, 0.24-2.89). A strong protective effect of tamoxifen was apparent among women who had undergone natural menopause (OR = 0.44; 95% CI, 0.27-0.65).Should tamoxifen be given to women with mutations who have had an oophorectomy? Clearly, more data are needed. In women over 50, or who had an oophorectomy after natural menopause, tamoxifen should be effective. In young women (<50) following surgical menopause, the data are less clear-cut, but I think the drug should be considered. Factors to take into consideration when making this decision should include the estimate of the residual lifetime risk of cancer, the woman's level of interest in mastectomy (there is no point in giving tamoxifen to healthy women after prophylactic mastectomy), the presence of an intact uterus (i.e., risk of endometrial cancer) and access to MRI screening facilities.