Endocrine therapy of metastatic breast cancer

Abstract

Over the past decade, endocrine therapy for metastatic breast cancer has changed significantly. For many years, tamoxifen was the gold standard endocrine therapy against which all other treatment modalities were compared. This distinction was founded on the superior tolerability associated with tamoxifen, in light of the similar efficacy seen with other endocrine manipulations. Attempts to improve tamoxifen's efficacy without compromising tolerability has led to the investigation of multiple new antiestrogens. Toremifene is a tamoxifen analog with similar efficacy and tolerability compared with tamoxifen, but provides an alternative to tamoxifen for hormonally sensitive patients with breast cancer. Other antiestrogens are currently under development, including the selective estrogen-receptor modulators idoxifene, raloxifene, and LY353381 and pure antiestrogens ICI 182780, ICI 164384, RU 58668, and EM-800. The luteinizing hormone-releasing hormone (LHRH) agonists are associated with similar efficacy compared with tamoxifen and oophorectomy in premenopausal women. Agents in this class of drugs include goserelin, leuprolide, and buserelin. The aromatase inhibitors are used in postmenopausal patients with breast cancer, in whom the primary source of estrogen production is limited to the peripheral conversion of androgen precursors to estrone and estradiol. Similar efficacy is seen between formestane and megestrol acetate (MA); however, formestane was inferior to tamoxifen with regard to efficacy. Anastrozole and letrozole appear to have similar efficacy and tolerability. Anastrozole administration results in superior overall survival compared with MA. With regard to letrozole, superior overall survival was seen compared with aminoglutethimide; however, a trend toward superior survival with letrozole compared with MA failed to reach statistical significance. Exemestane, a new steroidal aromatase inhibitor, may have efficacy despite previous exposure to tamoxifen or a nonsteroidal aromatase inhibitor. Other agents are used as salvage therapy for hormonally responsive metastatic breast cancer and include progestins and androgens. Combination endocrine therapy has been investigated over the years with little advantage over single-agent, sequential therapy. Newer data with combinations of LHRH agonists and tamoxifen or new generation aromatase inhibitors with tamoxifen are not yet available, but hold promise to change current approaches to therapy. Copyright (C) 2000 by W.B. Saunders Company.