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

Abstract

Since the identification of the novel transforming gene neu in rat neuroblastomas in 1981, and the subsequent cloning of the human equivalent HER-2, there have been considerable developments concerning the role and value of HER-2 in human breast cancer. Early studies found gene amplification in 20-30% of breast carcinomas, with most studies linking this to poorer survival. Numerous 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 present interest lies in the humanized monoclonal antibody against HER-2 (Herceptin) that has been developed. This is only of value if there is over-expression of HER-2 by a breast cancer, and so a reliable, accurate method of determination of HER-2 status is required. Immunohistochemistry is widely used and is relatively simple, with no major equipment requirements. However, there are variations in results with different antibodies and standardized methods, with controls for evaluating extent of reactivity required. Fluorescent in situ hybridization, which detects gene amplification, is an alternative approach that can be used with fixed embedded tissue but the technique is less widely available. HER-2 is the first oncoprotein involved in breast cancer in which there has been direct translation from the laboratory to the patient.