Breast cancer chemoprevention: beyond tamoxifen

A large number of new potential chemoprevention agents are available that t arget molecular abnormalities found in estrogen receptor (ER)-negative and/ or ER-positive precancerous breast tissue and have side effect profiles tha t differ from tamoxifen. Classes of agents currently undergoing evaluation in clinical prevention trials or those for which testing is planned in the near future include new selective ER modulators, aromatase inactivators/inh ibitors, gonadotrophin-releasing hormone agonists, monoterpenes, isoflavone s, retinoids, rexinoids, vitamin D derivatives, and inhibitors of tyrosine kinase, cyclooxygenase-2, and polyamine synthesis. New clinical testing mod els will use morphological and molecular biomarkers to select candidates at highest short-term risk, to predict the response to a particular class of agent, and to assess the response in phase II prevention trials. If validat ed, morphological and molecular markers could eventually replace cancer inc idence as an indicator of efficacy in future phase III trials.