Effects of the antiestrogens tamoxifen, toremifene, and ICI 182,780 on endometrial cancer growth

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1552-1558
Number of pages7
JournalJournal of the National Cancer Institute
Volume90
Issue number20
DOIs
StatePublished - Oct 21 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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