Tamoxifen: Toxicities and Drug Resistance During the Treatment and Prevention of Breast Cancer

Tamoxifen, a nonsteroidal antiestrogen, is the endocrine therapy of choice for all stages of breast cancer. There are six million women-years of experience with tamoxifen, and the drug has produced survival advantages in node-positive and node-negative patients who have had 2-5 years of adjuvant tamoxifen therapy. A low incidence of side effects has been reported with tamoxifen, resulting in the proposal to use the antiestrogen as a preventive agent for breast cancer. Three separate clinical trials are currently under way--in the United States, Italy, and the United Kingdom. Current concerns about tamoxifen are the development of rat liver tumors during long-term treatment and an increased incidence of endometrial carcinomas observed in patients. Another concern is the development of drug resistance to long-term tamoxifen therapy. There is increased interest in both determining the mechanism of drug resistance and evaluating new antiestrogens that may be more beneficial as a preventive, as an adjuvant therapy, or for the treatment of advanced breast cancer.