Melanie Spears1, John Bartlett. 1. University of Edinburgh, Edinburgh Cancer Research Centre, Crewe Road South, Edinburgh EH42XR, UK.
Abstract
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.
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.
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