Extending the clinical benefit of endocrine therapy for women with hormone receptor-positive metastatic breast cancer: differentiating mechanisms of action.

Principal goals of therapy for women with hormone receptor (HR)-positive metastatic breast cancer (MBC) are to maintain a good quality of life and to prolong survival; another important goal is to delay initiation of chemotherapy. Most women with tumors that are estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, or both are treated initially with endocrine therapy because of its effectiveness and relatively low toxicity. Several classes of single-agent endocrine therapies are available for postmenopausal women, including the nonsteroidal aromatase inhibitors (AIs), steroidal AIs, selective ER modulators, selective ER downregulators, progestins, androgens, and high-dose estrogen. In addition, combination therapy, either with 2 different endocrine agents or with endocrine therapy plus newer targeted therapies, provides some relatively new strategies for the treatment of these patients. Nevertheless, disease resistance ultimately develops with each endocrine regimen, and many questions remain regarding the optimal timing and sequencing of these treatments. This article reviews the efficacy and safety of endocrine therapy regimens in women with HR-positive MBC, and it addresses the effect of prior endocrine therapies and the mechanisms of action of the different endocrine regimens within the context of overall treatment goals.