Nuclear and extranuclear-initiated estrogen receptor signaling crosstalk and endocrine resistance in breast cancer

Estrogens regulate function of reproductive and non-reproductive tissues in healthy and diseased states including breast cancer. They mainly work through estrogen receptor alpha (ER alpha) and/or estrogen receptor beta (ER beta). There are various ER alpha targeting agents that have been used for treatment of ER (+) breast tumors. The impact of direct nuclear activity of ER is very well characterized in ER (+) breast cancers and development and progression of endocrine resistance. Recent studies also suggested important roles for extranuclear-initiated ER alpha pathways, which would decrease the potency and efficiency of ER alpha targeting agents. In this mini-review, we will discuss the role of nuclear and extra-nuclear ER signaling and how they relate to therapy resistance in breast cancer. (C) 2016 Elsevier Inc. All rights reserved.