Tamoxifen and Endometrial Cancer: From Experiment to Patient

Abstract

Tamoxifen, a nonsteroidal antiestrogen, is the treatment of choice for adjuvant therapy in breast cancer patients. It is currently used both as a palliative treatment for advanced disease and as an adjunct following surgery for node positive or negative disease (Jordan 1994). In addition, tamoxifen’s estrogen-like properties have been noted to reduce the incidence of fatal myocardial infarction (McDonald and Stewart 1991; Stewart and Everington 1992) and maintain bone density in postmenopausal patients (Love et al. 1992; Ward et al. 1993; Kristensen et al. 1994). These observations led to the concept of testing tamoxifen as a preventive agent in women with a high risk for breast cancer. Clinical trials that will each recruit about 20000 women volunteers are now proceeding in the United States, the United Kingdom and Italy (Powles et al. 1994; Vanchieri 1992; Fisher and Redmond 1991). However, in contrast to the beneficial effect on bones and lipids, the estrogenic actions of tamoxifen in the uterus have raised serious doubts about the safety of long-term therapy. Satyaswaroop et al. (1984) first described the partial stimulation by tamoxifen of a human endometrial carcinoma transplanted in athymic mice. Gottardis et al. (1988) cotransplanted a human breast carcinoma and a human endometrial carcinoma into athymic mice to determine whether tamoxifen would control the estrogen stimulated growth of both tumors. Tamoxifen inhibited the growth of the breast tumor but encouraged the growth of the endometrial carcinoma.