RISK OF ENDOMETRIAL CANCER AFTER TAMOXIFEN TREATMENT OF BREAST-CANCER

Since large trials have been set up to assess whether tamoxifen decrea ses the risk of breast cancer in healthy women, it has become importan t to investigate the drug's potential adverse effects, including occur rence of endometrial cancer. We undertook a case-control study in the Netherlands to assess the effect of tamoxifen on the risk of endometri al cancer after breast cancer. Through the population-based Netherland s Cancer Registry and two older, hospital-based, registries, we identi fied 98 patients who had endometrial cancer diagnosed at least 3 month s after a diagnosis of primary breast cancer. Detailed information abo ut treatment was obtained for all these patients, and for 285 controls , who were matched to the cases for age, year of breast cancer diagnos is, and survival time with intact uterus. Tamoxifen had been used by 2 4% of patients with subsequent endometrial cancer and 20% of controls (relative risk 1.3 [95% Cl 0.7-2.4]). Women who had used tamoxifen for more than 2 years had a 2.3 (0.9-5.9) times greater risk of endometri al cancer than never users. There was a significant trend of increasin g risk of endometrial cancer with duration of tamoxifen use (p=0.049), and also with cumulative dose (p=0.046). The duration-response trends were similar with daily doses of 40 mg or 30 mg and less. These findi ngs support the hypothesis that tamoxifen use increases the risk of en dometrial cancer. This oestrogenic effect on the endometrium was not r elated to the dose intensity. Physicians should be aware of the higher risk of endometrial cancer in tamoxifen users.