Antiestrogens as chemopreventive agents in breast cancer: Promise and issues in evaluation

Abstract

Tamoxifen citrate, the most extensively evaluated antiestrogen, acts primarily as a cytostatic agent by binding to the estrogen receptor. In rodent mammary model systems, when tamoxifen is given continuously after exposure to a carcinogen, the majority of expected tumors do not develop. In humans, adjuvant tamoxifen therapy, particularly when given for several years, is associated with significant improvement in relapse-free, and, in some studies, absolute survival. These benefits are achieved without major clinical toxicity and have led to suggestions that the use of tamoxifen as a chemopreventive agent in breast cancer be evaluated. In considering timing, optimal study population, study design, and methods for a chemoprevention trial using tamoxifen, the need for further data on the pharmacologic, biologic, and symptomatic effects of this agent becomes clear. Studies addressing this need are in progress and combined with ancillary data developed from ongoing adjuvant studies, should provide the critical information within the next few years.