EMERGING ROLE OF AROMATASE INHIBITORS IN THE TREATMENT OF BREAST-CANCER

The new generation of potent steroidal and nonsteroidal inhibitors of the enzyme aromatase act by decreasing estrogen production throughout the body in postmenopausal women. The most potent of these agents may also inhibit estrogen synthesis within metastatic breast cancer tissue . The newly developed, orally administered, nonsteroidal competitive i nhibitors, such as anastrozole (Arimidex), letrozole (Femara), and vor ozole (Rizivor), are a thousand times more potent inhibitors of aromat ase than is aminoglutethimide. Furthermore, these agents are highly se lective. In several large randomized trials, the new inhibitors produc ed similar response rates as megestrol acetate (160 mg/d) in postmenop ausal women with hormone-dependent breast cancer, but showed a trend t oward improved response duration and survival. They also produced less weight gain and fewer cardiovascular and thromboembolic side effects. In addition, letrozole proved superior to aminoglutethimide in anothe r randomized trial. Both anastrozole (1.0 mg/d) and letrozole (2.5 mg/ d) have now been approved as second-line treatment for hormone-depende nt breast cancer in postmenopausal women in whom disease has progresse d following tamoxifen treatment. Either drug should replace the routin e use of megestrol acetate in this setting. Ongoing clinical studies a re comparing anastrozole and letrozole to antiestrogens as first-line endocrine therapy for metastatic breast cancer. Other trials will stud y the possible roles of these compounds as adjuvant therapy and chemop revention for breast cancer.