Exemestane as first-line therapy in postmenopausal women with recurrent or metastatic breast cancer

Antiestrogen therapies generally offer significant disease control to hormone receptor-positive recurrent or metastatic breast cancer patients and are substantially better tolerated than standard chemotherapy regimens, thus representing an attractive first treatment option. The steroidal aromatase inhibitor (AI) exemestane exhibits antitumor effects by lowering full-body estrogen production in postmenopausal women and is an established treatment option for metastatic breast cancer. We review data from 2 recent phase III clinical trials that have confirmed exemestane activity in the first-line metastatic breast cancer setting, with moderate improvements in median progression-free survival (10-12 months) and objective response rates (37%-46%) compared with tamoxifen. The activity of first-line exemestane is comparable with other antiestrogen therapies, including fulvestrant and the nonsteroidal AIs letrozole and anastrozole. Additional findings demonstrating the clinical benefits of exemestane in women who previously progressed on nonsteroidal AIs highlight a partial lack of cross-resistance between these therapies and reinforce the opportunity to use multiple antiestrogen treatments sequentially. Future therapeutic developments in hormone receptor-positive metastatic breast cancer could include combinations with other targeted compounds plus AIs or other antiestrogen-based combinations and the identification of new strategies to evaluate differences among antiestrogen therapies to help optimize the treatment sequence and potential combinations.