Oestrogen receptors in breast cancer: basic mechanisms and clinical implications

Abstract

Since the discovery of the connection between ovarian hormones and breast cancer, endocrine therapy has been an integral adjuvant treatment for patients with hormone-dependent breast cancers. Oestrogen receptor (ER) plays a central role in mediating the effects of endogenous hormones and therapeutic agents. ER serves as a prognostic marker for responsiveness to endocrine therapy and is targeted either directly by selective oestrogen receptor modulators (SERMs) and pure antagonists or indirectly by aromatase inhibitors (AIs) that block oestrogen production. A significant number of ER-positive patients, however, fail to respond to therapy or develop resistance over time. This review focuses on the current understanding of ER functions and recent advances in genomic technologies and research that have provided a global perspective on hormone and ER activity and led to a number of significant discoveries, including the roles of co-regulatory factors and non-coding RNAs. Mechanistic insights into normal ER functions and therapeutic actions of SERMs and AIs will enable the development of better predictive markers and more effective target mechanisms and ultimately facilitate improvements in disease outcomes and patient survival.

Keywords: breast cancer; endocrine therapy; hormonal carcinogenesis; oestrogen receptor.

Figure 1.. Summary of molecular interactions and mechanisms involved in oestrogen signalling and oestrogen receptor functions. Each component represents potential markers and target mechanisms for endocrine therapy. ^*Targets of current endocrine therapeutics.