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JNCI Journal of the National Cancer Institute 1998 90(20):1552-1558; doi:10.1093/jnci/90.20.1552
© 1998 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 90, No. 20, 1552-1558, October 21, 1998
©Copyright 1998 Oxford University Press

ARTICLES

Effects of the Antiestrogens Tamoxifen, Toremifene, and ICI 182,780 on Endometrial Cancer Growth

Ruth M. O'Regan, Angela Cisnero, Gale M. England, Jennifer I. MacGregor, Henry D. Muenzner, Vasilios J. Assiki, Malcolm M. Bilimoria, Michael Piette, Yvonne P. Dragan, Henry C. Pitot, Robert Chatterton, V. Craig Jordan

Affiliations of authors: R. M. O'Regan (Division of Hematology/Oncology), A. Cisneros, J. I. MacGregor, H. D. Muenzner, V. J. Assikis, M. Piette, V. C. Jordan (Robert H. Lurie Comprehensive Cancer Center), G. M. England, M. M. Bilimoria (Department of Surgery), R. Chatterton (Department of Obstetrics and Gynecology), Northwestern University, Chicago, IL; Y. P. Dragan, H. C. Pitot, McArdle Laboratory, University of Wisconsin, Madison.

Correspondence to: V. Craig Jordan, Ph.D., D.Sc., Robert H. Lurie Comprehensive Cancer Center and Northwestern University Medical School, 8258 Olson, 303, E. Chicago Ave., Chicago, IL 60611.

Abstract

Background: Tamoxifen has been shown to promote the growth of human endometrial tumors implanted in athymic mice, and it has been associated with a twofold to threefold increase in endometrial cancer. Toremifene, a chlorinated derivative of tamoxifen, and ICI 182,780, a pure antiestrogen, 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 toremifene and ICI 182,780 on the growth of human endometrial cancer in athymic mice. Methods: Athymic, ovariectomized mice were implanted with human endometrial tumors and treated with estrogen, tamoxifen, or the new antiestrogens. Results: The effects of tamoxifen and toremifene on the growth of either tamoxifen-stimulated or tamoxifen-naive endometrial tumors in athymic mice were not substantially different. ICI 182,780 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 models. Therefore, it is possible that toremifene, like tamoxifen, may be associated with an increased incidence of endometrial cancer. In contrast, ICI 182,780 inhibited tamoxifen-stimulated endometrial cancer, both in the presence and in the absence of estrogen, suggesting that this 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 incidence of endometrial cancer. Indeed, it is even possible that ICI 182,780 may prove useful as an adjuvant agent in early stage endometrial cancer. [J Natl Cancer Inst 1998;90:1552-8]


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