Hormonal therapies of metastatic breast cancer: the past and the present

Abstract

Endocrine therapy of metastatic breast cancer has been established for more than a century. Following the discovery of the beneficial effects of oophorectomy by Beatson in 1896 and the identification of the first estrogen receptor (ER- ) by E. Jensen 70 years later (1967), antihormonal treatment of breast cancer represented not only the first systemic treatment strategy in oncology but also the first for which a clear scientific rationale has been established. While early treatment options (either surgical or additive drug treatment) were associated with significant side effects, the partial estrogen receptor antagonist tamoxifen established modern endocrine drug therapy of metastatic breast cancer. The compound became the most widely used drug in breast cancer therapy until now. Recently, the role of tamoxifen has been challenged following development of other novel, highly potent, and selective drugs. The most important improvement has certainly been made with the implementation of the third generation of aromatase inhibitors (anastrozole, letrozole, and exemestane). These compounds are now in general used as first-line therapy in metastatic breast cancer in postmenopausal women not exposed to the compounds in the adjuvant setting for those relapsing after adjuvant therapy with an aromatase inhibitor. In addition, SERDs (selective estrogen receptor downregulators) like fulvestrant have shown clinical efficacy and have been introduced in standard care as well. The present publication provides an overview about endocrine treatment options of metastatic breast cancer and discusses possible treatment algorithms for both pre-and postmenopausal breast cancer patients.