Estrogen receptor alpha negative breast cancer patients: Estrogen receptor beta as a therapeutic target

Clinical management of breast cancer is increasingly guided by assessment of tumor phenotypic parameters. One of these is estrogen receptor (ER) status, currently defined by ER alpha expression. However with the discovery of a second ER, ER beta and its variant isoforms, the definition of ER status is potentially more complex. In breast tumors there are two ER beta expression cohorts. One where ER beta is co-expressed with ER alpha and the other expressing ER beta alone. In the latter subgroup of currently defined ER negative patients ER beta has the potential to be a therapeutic target. Characterization of the nature and role of ER beta in ER alpha negative tumors is essentially unexplored but available data suggest that the role of ER beta may be different when co-expressed with ER alpha and when expressed alone. This review summarizes available data and explores the possibility that ER beta signaling may be a therapeutic target in these tumors. Evidence so far supports the idea that the role of ER beta in breast cancer is different in ER(x negative compared to ER alpha positive tumors. However, cohort size and numbers of independent studies are small to date, and more studies are needed with better standardization of antibodies and protocols. Also, the ability to determine the role of ER beta in ER alpha negative breast cancer and therefore assess ER beta signaling pathways as therapeutic targets would be greatly facilitated by identification of specific downstream markers of ER beta activity in breast cancer. (C) 2007 Elsevier Ltd. All rights reserved.