Dowsett M
Department of Biochemistry, Royal Marsden Hospital, London SW3 6JJ, UK.
Endocr Relat Cancer. 2001 Sep;8(3):191-5. doi: 10.1677/erc.0.0080191.
Hormonal therapy leads to improved survival in oestrogen receptor (ER) positive early breast cancer and long-term responses in advanced disease. However, resistance to such therapy is a serious clinical problem. This article considers the data for and against there being a significant role for the oncogene HER-2 in such resistance. Transfection of HER-2 into MCF-7 cells leads to resistance to tamoxifen but data differ in relation to the oestrogen dependence of such cells. A number of retrospective studies have been conducted of HER-2 status in adjuvant trials of tamoxifen. Most of these also suggest a negative role but individually the studies do not have the statistical power to be conclusive. Recent studies in the neoadjuvant context have shown a significant antiproliferative effect of endocrine therapy in HER-2 positive/ER positive tumours but this is much less than in HER-2 negative/ER positive tumours. It is concluded that incomplete hormonal resistance results from co-expression of HER-2 and ER and that this may differ between different hormonal agents.
激素疗法可提高雌激素受体（ER）阳性早期乳腺癌患者的生存率，并使晚期疾病产生长期缓解。然而，对这种疗法的耐药性是一个严重的临床问题。本文探讨了支持和反对癌基因HER-2在这种耐药性中起重要作用的数据。将HER-2转染到MCF-7细胞中会导致对他莫昔芬产生耐药性，但关于此类细胞对雌激素的依赖性的数据存在差异。在他莫昔芬辅助治疗试验中，已经对HER-2状态进行了多项回顾性研究。其中大多数研究也表明其具有负面作用，但个别研究没有足够的统计效力得出结论。近期在新辅助治疗背景下的研究表明，内分泌治疗对HER-2阳性/ER阳性肿瘤具有显著的抗增殖作用，但远低于HER-2阴性/ER阳性肿瘤。得出的结论是，HER-2和ER的共表达导致了不完全的激素耐药性，并且这在不同的激素药物之间可能有所不同。
