Spears Melanie, Bartlett John
University of Edinburgh, Edinburgh Cancer Research Centre, Crewe Road South, Edinburgh EH42XR, UK.
Expert Opin Ther Targets. 2009 Jun;13(6):665-74. doi: 10.1517/14728220902911509.
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.
乳腺癌有多种亚型，主要包括雌激素受体（ER）阳性的腔面A型和B型。激素治疗的治疗选择基于ER表达。虽然对于ER阳性癌症，内分泌治疗在辅助治疗中非常成功，但相当一部分癌症表现出激素抵抗，这通常与生长因子受体或ER信号改变有关。受体共激活因子或共抑制因子对类固醇受体功能的调节是一种潜在的抵抗机制。共激活因子的p160或SRC原癌基因家族在乳腺癌对内分泌治疗的反应中很重要，并且可以作为共激活因子功能的范例。
目的/方法：本综述重点关注ER和ER共激活因子在乳腺癌中的作用，以及目前针对SRC辅助因子治疗激素受体阳性乳腺癌的方法。
结果/结论：基于对他莫昔芬治疗耐药的风险或生物学证据，有一种选择性应用芳香化酶抑制剂的趋势。这两种策略都可能提高治疗效益比。
