Aromatase inhibitors for chemoprevention.

Pre-clinical, molecular and epidemiological evidence supports a role for estrogen in both the initiation and promotion of breast cancer. Antagonizing estrogen has therefore been proposed as one way of reducing risk. Tamoxifen, which competes with estrogen at the estrogen receptor, has been shown in four phase III clinical trials to reduce tumour occurrence substantially. Aromatase inhibitors are superior to tamoxifen in terms of both efficacy and toxicity in advanced disease and in the neoadjuvant and adjuvant setting. Exemestane may be distinct because its steroidal structure potentially protects bone and lipid metabolism from estrogen ablation. Phase three trials are ongoing to test the efficacy of the inhibitors, including the IBIS 2 trial which randomizes anastrozole against placebo and the NCIC CTG MAP.3 study of exemestane with or without celecoxib against placebo. The efficacy and toxicity results of these studies, and the identification of risk profiles from them, are awaited with interest.