Consequences of the Convergence of Multiple Alternate Pathways on the Estrogen Receptor in the Treatment of Metastatic Breast Cancer.

Endocrine therapy is the usual first-line therapy for patients with hormone receptor-positive metastatic breast cancer. However, resistance to hormone therapies frequently occurs during the course of treatment. Growing understanding of the signal cascade of estrogen receptors and the signaling pathways that interact with estrogen receptors has revealed the complex role of these receptors in cell growth and proliferation, and on the mechanism in development of resistance. These insights have led to the development of targeted therapies that may prove to be effective options for the treatment of breast cancer and may overcome hormone therapy resistance. This article reviews current understanding of the cellular receptor signaling pathways that interact with estrogen receptors. It also reviews data from recent ongoing clinical trials that examine the effects of targeted therapies, which might interfere with estrogen receptor pathways and might reduce or reverse resistance to traditional, sequential, single-agent endocrine therapy.