TAMOXIFEN - TOXICITIES AND DRUG-RESISTANCE DURING THE TREATMENT AND PREVENTION OF BREAST-CANCER

Tamoxifen, a nonsteroidal antiestrogen, is the endocrine therapy of ch oice for all stages of breast cancer. There are six million women-year s of experience with tamoxifen, and the drug has produced survival adv antages in node-positive and node-negative patients who have had 2-5 y ears of adjuvant tamoxifen therapy. A low incidence of side effects ha s been reported with tamoxifen, resulting in the proposal to use the a ntiestrogen as a preventive agent for breast cancer. Three separate cl inical trials are currently under way-in the United States, Italy, and the United Kingdom. Current concerns about tamoxifen are the developm ent of rat liver tumors during long-term treatment and an increased in cidence of endometrial carcinomas observed in patients. Another concer n is the development of drug resistance to long-term tamoxifen therapy . There is increased interest in both determining the mechanism of dru g resistance and evaluating new antiestrogens that may be more benefic ial as a preventive, as an adjuvant therapy, or for the treatment of a dvanced breast cancer.