Several large phase III trials have demonstrated that
tamoxifen-and more recently,
raloxifene-can effectively reduce the incidence of invasive
breast cancer by 50%. However, these
selective estrogen receptor modulators can also be associated with several rare, but serious, adverse events. Recently, the third-generation
aromatase inhibitors (AIS) have demonstrated excellent efficacy in adjuvant
breast cancer trials, and they show particular promise in the
breast cancer prevention setting. The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) has developed a randomized phase III study to determine the efficacy of an ai (
exemestane) to reduce the incidence of invasive
breast cancer in postmenopausal women at an increased risk for developing
breast cancer. The NCIC CTG map.3 (ExCel) trial is a double-blind placebo-controlled multicentre, multinational trial. Based on the known preclinical and clinical profile of the ais, a greater reduction in
breast cancer incidence with fewer side effects is hypothesized with this class of agents than with
tamoxifen or
raloxifene.