Uterine carcinosarcomas in patients receiving tamoxifen. A report of 19 cases.

Uterine carcinosarcomas are highly aggressive neoplasms with a tendency to early extrauterine spread, high stage at diagnosis, and a poor prognosis. Tamoxifen is widely used as adjuvant therapy in the treatment of breast cancer and is known to cause endometrial proliferative lesions, including adenocarcinoma. In recent years, there have been occasional reports of uterine carcinosarcoma in patients taking tamoxifen. The aim of this study is to describe the clinicopathologic profile in 19 women taking tamoxifen who subsequently developed uterine carcinosarcoma. Nineteen patients were identified from cases of uterine carcinosarcoma diagnosed at three institutions. The case notes were examined and the pathology reviewed. The age at diagnosis of carcinosarcoma ranged from 47 to 91 years (mean 71 years). All patients were postmenopausal and received 20 mg tamoxifen daily; the duration of treatment ranged from 1 to 15 years (mean 7.1 years). The cumulative dose of tamoxifen ranged from 7.3 to 109.5 g. Ten tumors were stage I, one stage II, seven stage III, and one stage IV. Ten of the carcinosarcomas were homologous, and nine contained heterologous elements in the form of rhabdomyoblasts (six cases) or malignant cartilage (three cases). The overall prognosis was extremely poor. Fifteen patients died within 35 months of the diagnosis of carcinosarcoma (mean 12 months). Two patients are alive with very short follow-up periods, and two were lost to follow-up. The reported data support an association between tamoxifen therapy and the development of uterine carcinosarcoma. The risk is likely to be highest in those patients who have been taking tamoxifen for a prolonged period. A majority of tumors in the present study were stage I, and this suggests that uterine carcinosarcomas in patients taking tamoxifen may be diagnosed at an earlier stage than those arising de novo. However, the prognosis was still poor even with low-stage disease. Properly controlled epidemiological studies are necessary to confirm an association between tamoxifen and uterine carcinosarcoma.