Aromatase inhibitors for breast cancer in postmenopausal women

Abstract

Third-generation aromatase inhibitors are potent inhibitors of the aromatase enzyme, which catalyzes the last step in estrogen biosynthesis. These agents are active against breast cancer in hormone-naïve postmenopausal women and in women who have experienced failure of tamoxifen or failure of tamoxifen plus other hormonal therapy. There are two types of aromatase inhibitors, irreversible steroidal activators (e.g., exemestane) and reversible nonsteroidal imidazole-based inhibitors (e.g., anastrozole, letrozole). Recent data suggest that some women who experience failure of one type of aromatase inhibitor can subsequently derive benefit from the other type. The reason for this lack of cross-resistance is unknown. This finding of non-cross-resistance between steroidal aromatase activators and nonsteroidal aromatase inhibitors offers the opportunity to increase the number of lines of hormone therapy before making the inevitable switch to more toxic chemotherapy, thus potentially improving quality of life for postmenopausal women with advanced disease. Data from postmenopausal women with advanced disease suggest that steroidal and nonsteroidal aromatase inhibitors have similar tolerability profiles; however, emerging data suggest that there may be differences in their effects on end organs, which may become evident with longer term use, such as in the adjuvant or prevention settings. Steroidal agents appear to have beneficial effects on lipid and bone metabolism, whereas nonsteroidal agents may have neutral or unfavorable effects. These differences may be attributed to the androgenic effects of steroidal agents; clinical trials are currently under way to confirm these suspicions.