The incidence of subsequent endometrial carcinoma with tamoxifen use in patients with primary breast carcinoma

Abstract

Background: Tamoxifen commonly is used as adjuvant therapy for all stages of breast carcinoma. However, several studies have suggested an association between the use of tamoxifen in breast carcinoma patients and the subsequent development of endometrial carcinoma. The objective of this study was to determine the relation between long term tamoxifen usage and the risk of endometrial carcinoma in patients with breast carcinoma and to determine whether the increase in the cumulative incidence of endometrial carcinoma observed in previous studies is a true increase.

Methods: Eight hundred and twenty-five patients with primary breast carcinoma who underwent annual gynecologic examination and cancer screening were reviewed. None of the patients had undergone hysterectomy or received any prior estrogen replacement therapy. These patients underwent a pelvic examination and cytologic and/or histologic screening of the cervix and endometrium every year even if they had no gynecologic symptoms. The dose of tamoxifen, length of tamoxifen treatment, and potential confounding variables were recorded. The relative risk of subsequent endometrial carcinoma in patients with primary breast carcinoma was analyzed by the Cox proportional hazards model.

Results: Thirteen of the 825 patients developed a subsequent endometrial carcinoma. The cumulative incidence of endometrial carcinoma was 1.58%. Four of 13 patients who subsequently developed endometrial carcinoma received tamoxifen and 9 had not received tamoxifen. The relative risk of endometrial carcinoma by total dose of tamoxifen exposure was 1.0001 (P = 0.0145). There was no statistically significant correlation between the cumulative dose of tamoxifen or the length of tamoxifen treatment and the histologic type and grade of endometrial carcinoma. In addition, there was no statistical difference in the prognosis of endometrial carcinoma between the patients who received tamoxifen and patients who did not.

Conclusions: The results of this study show that tamoxifen use does not appear to increase the incidence of subsequent endometrial carcinoma in patients with primary breast carcinoma who underwent annual screening for gynecologic carcinoma.