Effect of low-dose tamoxifen on benign gynecological and breast conditions in a phase 3 trial in noninvasive breast cancer.

Despite the proven efficacy of tamoxifen in breast cancer prevention, its uptake remains limited due to concerns over side effects. A phase 3 trial showed that low-dose tamoxifen (5 mg/d for 3 years) substantially reduces recurrence with minimal toxicity. After 10 years of follow-up, we observed no clinically significant differences in benign gynecological or breast events between the tamoxifen and placebo arms. The uterus was the most frequently affected site (30 cases per arm), followed by the breast (18 cases) and ovary (5 cases vs 3 cases for tamoxifen and placebo, respectively). Endometrial polyps were similarly distributed. Endometrial thickness remained stable in premenopausal women and showed only a mild, non-clinically significant increase in postmenopausal women on tamoxifen (approximately 1.5 mm). Compared with data on standard-dose tamoxifen, rates of benign events were lower. These findings reinforce the favorable safety profile of low-dose tamoxifen.