Methods: The hospital and office records of patients treated with tamoxifen at the University of Kansas Medical Center and Research Medical Center were analyzed. A comprehensive review of tamoxifen in the English and European literature was performed using MEDLINE and the bibliographies of various articles.

Results: From 1985-1992 at our institutions, six tamoxifen-treated breast cancer patients developed gynecologic tumors: three endometrial adenocarcinomas, a mixed mullerian sarcoma, a fallopian tube carcinoma with adenofibroma of the endometrium, and recurrent hyperplastic endometrial polyps. The literature contained 61 cases of adenocarcinoma of the endometrium and possibly four cases of uterine sarcomas in tamoxifen-treated breast cancer patients. The number of gynecologic malignancies reported is now 70. In 35 of the patients, the mean age (+/- standard deviation) was 63.9 +/- 12.0 years, and 61 of 66 patients (92.4%) were postmenopausal. Of the endometrial adenocarcinomas, 25 of 27 (92.6%) were stage I, and 11 of 27 (40.7%) were grade 1. The dose of tamoxifen was 20 mg/day in 15 (23.4%), 30 mg/day in 11 (17.2%), and 40 mg or higher in 38 (59.4%); 57% were treated with tamoxifen for less than 2 years.

Conclusions: Tamoxifen is a safe and reliable treatment of breast cancer, but data suggest an association with endometrial cancer. We propose close monitoring of patients taking tamoxifen and prompt evaluation of any uterine bleeding or pelvic complaint.