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Questions about Tamoxifen and the Future Use of Antiestrogens

Department of Surgery and the Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago, Illinois, USA

Correspondence: V. Craig Jordan, Ph.D., D.Sc., Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, 303 E. Chicago Avenue, 8258 Olson Pavilion, Chicago, Illinois 60611, USA. Telephone: 312-908-4148; Fax: 312-908-1372.

Tamoxifen is the most widely prescribed anticancer drug in the world. It not only improves overall survival and decreases recurrence from breast cancer, but has beneficial effects on bone density and lipid profiles. Unfortunately, tamoxifen carries disadvantages such as unpleasant side effects and a questionable connection to endometrial carcinoma. However, after intense debate, the general consensus among the medical community is that the benefits of tamoxifen far outweigh the risks. Nonetheless, resistance to tamoxifen has been seen both in the clinic and in the laboratory prompting investigators to look for new antiestrogens in the treatment and prevention of breast cancer. We report on three agents: toremifene (Fareston^®), ICI 182, 780 (Faslodex^®), and raloxifene (Evista^®). Unfortunately, clinical studies comparing tamoxifen and toremifene in the treatment of breast cancer have not shown a clear advantage of toremifene over tamoxifen. ICI 182, 780 is a "pure antiestrogen" that carries a low incidence of side effects and may hold promise as an effective agent for patients who have failed tamoxifen therapy or even as primary adjuvant therapy. Raloxifene displays beneficial bone and cardiovascular effects without uterine stimulation. It is being used as an agent to prevent osteoporosis and holds promise as an agent for advanced breast cancer. We hope that these new antiestrogens will revolutionize the way we treat breast cancer.

Key Words. Antiestrogens • Tamoxifen • Toremifene • ICI 182,780 • Tamoxifen resistance • Endometrial carcinoma

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