Other Hormonal Approaches

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Several other hormonal therapies have activity against metastatic breast cancer and have been evaluated as adjuvant therapy in early disease. Toremifene (Fareston) is a derivative of tamox-ifen with a similar mechanism of action and activity against disseminated disease.7 It is being evaluated in randomized trials against tamoxifen as adjuvant therapy in older women. Progestins lower endogenous estrogen levels in postmenopausal women and cause tumor regression in many women with advanced disease.7 Medroxyprogesterone has been studied as adjuvant therapy in randomized trials, with negative results.41,42 Aromatase inhibitors (AI) inhibit the enzyme that catalyzes the conversion of androgen to estrogen. They, too, lower serum (and intracellular) estrogen levels in older women and are effective hormonal therapies of metastatic breast cancer.7 Aminog-lutethimide, one of the first-generation aro-matase inhibitors, however, was no better than placebo in an adjuvant trial after surgery in postmenopausal women.43 New classes of more potent and selective aromatase inhibitors have been recently introduced for the treatment of advanced disease and are being evaluated as adjuvant therapy. The ATAC trial is a multinational randomized double-blinded study in postmenopausal women of adjuvant tamoxifen versus the new AI anastrozole (Arimidex) versus the combination for 5 years. Another trial looks at women that have received 5 years of tamoxifen and are then being randomized to no further therapy or treatment with the AI letro-zole (Femara). The results of the toremifene, arimidex, and letrozole trials and a European trial of the AI formestane are not yet known. To date, other than tamoxifen and oophorec-tomy, there are no standard hormonal adjuvant therapies.

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