Endocrine therapy of breast cancer

Abstract

Endocrine therapies for breast cancer have been used for more than a century. Several endocrine agents have been developed in recent years: estrogens, androgens, progestins, anti-estrogens, aromatase inhibitors, gonadotropin-releasing hormone analogs, antiprogestins, and antiandrogens. The use of some of these agents in advanced disease led to investigations in early breast cancer. Tamoxifen was the drug which was most extensively tested, showing a significant long-term survival benefit for treated patients. Progestins (medroxyprogesterone acetate) and aromatase inhibitors (aminoglutethimide) were also tested in a few clinical trials, but no conclusive recommendations for their use in patients with operable disease may be formulated. The most important current challenges for the appropriate use of endocrine therapies in breast cancer include: understanding the effect of endocrine therapies and the mechanisms of resistance associated with their use; development of new agents with novel endocrine antitumor effect; defining the best way to combine endocrine agents with cytotoxics or with other endocrine manipulations; and identifying long-term effects of endocrine agents in terms of disease control and prevention, as well as desirable and undesirable side effects.