The potential role of estrogen receptors and the SRC family as targets for the treatment of breast cancer

Background: Breast cancer has a number of subtypes, the main ones are estrogen-receptor (ER)-positive, luminal type A and B. Treatment selection, with respect to hormonal therapy, is based upon ER expression. Whilst for ER-positive cancers, endocrine therapy is highly successful in the adjuvant setting, a significant proportion of cancers exhibit hormone resistance, often associated with altered growth factor receptor or ER signalling. Modulation of steroid receptor function by receptor co-activators or repressors is a potential mechanism of resistance. The p160 or SRC proto-oncogene family of co-activators are important in breast cancer response to endocrine therapy and can act as a paradigm of co-activator function. Objective/methods: This review focuses on the role of ER and ER co-activators in breast cancer and current approaches to targeting SRC co-factors for treatment of hormone-receptor-positive breast cancer. Results/conclusions: There is a drive to selectively apply aromatase inhibitors on the basis of either risk or biological evidence of resistance to tamoxifen treatment. Both strategies may yield improved treatment to benefit ratios.