Strategies for breast cancer therapy with antiestrogens.
Current clinical research is focused upon the application of adjuvant therapy for the treatment of breast cancer. Combination chemotherapy is the most successful adjuvant therapy for premenopausal patients whereas the antiestrogen tamoxifen (1 or 2 yr) is successful in postmenopausal disease. We have developed a unifying strategy for the treatment of breast cancer. The thesis is based upon the application of continuous adjuvant therapy with tamoxifen in a low estrogen environment. Chemotherapy causes a chemical castration in premenopausal patients. In contrast, tamoxifen causes an increase in steroidogenesis. A combination of both approaches will work against each other until ovarian failure occurs. Patients should be checked for castration to provide a low estrogen environment in which tamoxifen, a competitive antagonist of estrogen action, can effectively work. Laboratory evidence using carcinogen-induced rat mammary tumor models demonstrates the efficacy of long-term therapy. Studies with the human breast cell line MCF-7 grown in athymic mice show that tamoxifen is a tumoristatic agent so that once the therapy is stopped, tumors can be regrown by estrogen administration. Patients should receive continuous tamoxifen therapy to prevent the growth-stimulating effects of adrenal steroids, environmental and phyto-estrogens.
Jordan
V C
VC
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
Fritz
N F
NF
Gottardis
M M
MM
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000517:prevention & control / Q000601:surgery; D003131:Combined Modality Therapy; D004347:Drug Interactions; D004965:Estrogen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D008593:Menopause; D051379:Mice; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000601:surgery; D010052:Ovariectomy; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013629:Tamoxifen / Q000627:therapeutic use
D004965:Estrogen Antagonists; D004967:Estrogens; D013629:Tamoxifen