IATROGENIC RISKS OF ENDOMETRIAL CARCINOMA AFTER TREATMENT FOR BREAST-CANCER IN A LARGE FRENCH CASE-CONTROL STUDY

Since tamoxifen is widely used in breast cancer treatment and has been proposed for the prevention of breast cancer, its endometrial iatroge nic effects must be carefully examined. We have investigated the assoc iation between endometrial cancer and tamoxifen use or other treatment s in women treated for breast cancer in a case-control study. Cases of endometrial cancer diagnosed after breast cancer (n = 135) and 467 co ntrols matched for age, year of diagnosis of breast cancer and hospita l and survival time with an intact uterus were included. Women who had received tamoxifen were significantly more likely to have endometrial cancer diagnosed than those who had not (crude relative risk = 4.9, p = 0.0001). Univariate and adjusted analyses showed that the risk incr eased with the length of treatment (p = 0.0001) or the cumulative dose of tamoxifen received (p = 0.0001), irrespective of the daily dose. W omen who had undergone pelvic radiotherapy also had a higher risk (cru de relative risk = 7.8, p = 0.0001). After adjusting for confounding f actors, the risk was higher for tamoxifen users (p = 0.0012), treatmen t for more than 3 years (all p < 0.03) and pelvic radiotherapy (p = 0. 012), Women who had endometrial cancer and had received tamoxifen had more advanced disease and poorer prognosis than those with endometrial cancer who had not received this treatment. Our results suggest a cau sal role of tamoxifen in endometrial cancer, particularly when used as currently proposed for breast cancer prevention, Pelvic radiotherapy may be an additional iatrogenic factor for women with breast cancer. E ndometrial cancers diagnosed in women treated with tamoxifen have poor er prognosis. Women who receive tamoxifen for breast cancer should be offered gynaecological surveillance during and after treatment. A long -term evaluation of the risk-benefit ratio of tamoxifen as a preventiv e treatment for breast cancer is clearly warranted. (C) 1998 Wiley-Lis s, Inc.