Gynecologic effects of tamoxifen and the association with endometrial carcinoma

Tamoxifen has been used as an adjuvant therapy for breast cancer for nearly two decades. The benefits of adjuvant tamoxifen therapy in prolonging disease-free and overall survival have been shown in randomized clinical trials. Despite this, some developing evidence suggests that tamoxifen causes a 2- to 3-fold increase in endometrial cancer. This paper reviews the reports of endometrial carcinoma in tamoxifen-treated patients. Two hundred fifty cases of endometrial carcinoma are reported, but only one case is identified in a premenopausal woman. When documented, 77% (n=127) of the cases are good-grade (grade 1 or 2) and 80% (n=125) are stage-I disease. Since the distribution of good grade (79%) and stage I (74%) from the Surveillance, Epidemiology and End Results (SEER) data are comparable, concerns about more aggressive or late-stage disease appear to be unwarranted. The modest increase in the incidence of early-stage, good-grade endometrial carcinoma described during tamoxifen therapy suggests that it would be unreasonable to institute an aggressive detection strategy of endometrial biopsies. This approach would only lead to further detection bias and would not be cost-effective. Physicians should ensure that patients do not have pre-existing endometrial cancer prior to adjuvant tamoxifen therapy for breast cancer and, furthermore, they should educate patients about signs and symptoms of early endometrial carcinoma and when reported these should be followed up with a gynecologic examination.