Overexpression of HER-2 as a resistance mechanism to hormonal therapy for breast cancer.
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.
Dowsett
M
M
Department of Biochemistry, Royal Marsden Hospital, London SW3 6JJ, UK. mitch@icr.ac.uk
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
D018931:Antineoplastic Agents, Hormonal; D018719:Erb-b2 Receptor Tyrosine Kinases