EFFECTS OF THE ANTIESTROGENS TAMOXIFEN, TOREMIFENE, AND ICI-182,780 ON ENDOMETRIAL CANCER GROWTH

Background: Tamoxifen has been shown to promote the growth of human en dometrial tumors implanted in athymic mice, and it has been associated with a twofold to threefold increase in endometrial cancer. Toremifen e, a chlorinated derivative of tamoxifen, and ICI 182,780, a pure anti estrogen, are two new antiestrogens being developed for the treatment of breast cancer. The effects of these drugs on endometrial cancer are currently unknown. Our objective was to evaluate the effects of torem ifene and ICI 182,780 on the growth of human endometrial cancer in ath ymic mice. Methods: Athymic, ovariectomized mice were implanted with h uman endometrial tumors and treated with estrogen, tamoxifen, or the n ew antiestrogens. Results: The effects of tamoxifen and toremifene on the growth of either tamoxifen-stimulated or tamoxifen-naive endometri al tumors in athymic mice were not substantially different. ICI 182,78 0 inhibited the growth of tamoxifen-stimulated endometrial cancer, in both the presence and the absence of estrogen, Conclusions: Toremifene and tamoxifen produce identical effects in our endometrial cancer mod els. Therefore, it is possible that toremifene, like tamoxifen, may be associated with an increased incidence of endometrial cancer. In cont rast, ICI 182,780 inhibited tamoxifen-stimulated endometrial cancer, b oth in the presence and in the absence of estrogen, suggesting that th is drug may be safe with regard to the endometrium, even if it is used following tamoxifen, and that it may not result in an increased incid ence of endometrial cancer. Indeed, it is even possible that ICI 182,7 80 may prove useful as an adjuvant agent in early stage endometrial ca ncer.