Pure antiestrogens as a new therapy for breast cancer.
Tamoxifen is the endocrine therapy of choice for all stages of breast cancer. However, the drug cannot be considered to be a cure as drug resistance will eventually develop. The resistance can take two forms: either the loss of estrogen receptor or the selection of estrogen receptor positive disease that is tamoxifen stimulated for growth. Laboratory studies have demonstrated that tamoxifen-stimulated MCF-7 breast tumors can develop in athymic mice. A number of pure (nonestrogenic) antiestrogens have been discovered that can either be administered by injection (e.g., ICI 182,780) or orally (e.g., EM-800). In preliminary clinical studies, the compound ICI 182,780 (Faslodex) has been shown to be an effective second-line therapy after tamoxifen failure. The goal of future clinical studies is to evaluate the therapeutic efficacy and patient acceptability of aromatase inhibitors (postmenopausal estrogen withdrawal), and injectable or oral pure antiestrogens after the failure of long-term tamoxifen therapy. Clearly, the primary purpose for the treatment of advanced breast cancer is to control disease growth; nevertheless, an evaluation of the effect of new agents on bones and lipids is required before pure antiestrogens could be considered for adjuvant therapy.
England
G M
GM
Department of Surgery, Northwestern University Medical School, Chicago, IL 60611, USA.
Jordan
V C
VC
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D051379:Mice; D013629:Tamoxifen / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D013629:Tamoxifen