Aromatase inhibition and antiestrogen therapy in early breast cancer treatment and chemoprevention

The aromatase inhibitors represent an important class of hormonal agents for the management of breast cancer. The third-generation aromatase inhibitors have replaced megestrol acetate as second-line hormonal therapy in advanced breast cancer, and large clinical trials are maturing to establish their efficacy relative to tamoxifen (Nolvadex) in the first-line metastatic setting. The increased potency, increased specificity, and established efficacy of aromatase inhibitors in advanced breast cancer have provided the rationale for a large number of randomized trials in the adjuvant setting evaluating anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara). These trials are addressing the value of these agents in sequence with, instead of, and in combination with tamoxifen. The relationship between estrogen exposure and breast cancer risk has long been accepted and traditionally related to estrogen-receptor-mediated events. The emergence of the estrogen genotoxicity hypothesis as a mechanism for breast cancer carcinogenesis provides additional rationale for considering aromatase inhibitors in the chemoprevention setting.