The significance of histological determination of HER-2 status in breast cancer

Since the identification of the novel transforming gene neu in rat neurobla stomas in 1981, and the subsequent cloning of the human equivalent HER-2, t hen have been considerable developments concerning the role and value of HE R-2 in human breast cancer. Early studies found gene amplification in 20-30 % of boast carcinomas, with most studies linking this to poorer survival. N umerous antibodies have been generated against the oncoprotein and in many instances overexpression, as defined by membrane staining of breast cancer cells, correlated with gene amplification. Many studies, but not all, have found an association between HER-2 reactivity and poor prognosis. HER-2 can also be detected in high-grade ductal carcinoma in situ. HER-2 status can also aid prediction of response to hormonal and chemotherapy, but the prese nt interest lies in the humanized monoclonal antibody against HER-2 (Hercep tin(R)) that has been developed. This is only of value if there is over-exp ression of HER-2 by a breast cancer, and so a reliable, accurate method of determination of HER-2 status is required. Immunohistochemistry is widely u sed and is relatively simple, with no major equipment requirements. However , there are variations in results with different antibodies and standardize d methods, with controls for evaluating extent of reactivity required. Fluo rescent in situ hybridization, which detects gene amplification, is an alte rnative approach that can be used with fixed embedded tissue but the techni que is less widely available. HER-2 is the first oncoprotein involved in br east cancer in which there has been direct translation from the laboratory to the patient. (C) 2000 Harcourt Publishers Ltd.