Clinical relevance of HER-2 amplification and overexpression in human cancers

The human epidermal growth factor receptor 2 (HER-2) is amplified or otherwise overexpressed in 20-30% of invasive carcinomas of the breast. This overexpression has been associated with a poor prognosis in breast cancer patients, particularly those having involvement of the axilary lymph nodes. The most commonly used techniques for determining the HER-2 status of a tumor are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). In addition, the HER-2 extracellular domain can be detected in the serum of metastatic breast cancer patients using an enzyme-linked immunosorbant assay (ELISA). HER-2 overexpression has been associated with resistance to chemotherapy and hormone therapy. Trastuzumab, a monoclonal antibody directed against the extracellular domain of the HER-2 protein, is an effective therapy for patients with HER-2 overexpressing tumors, either alone or in combination with chemotherapy. Patients whose tumors express high levels of HER-2 as detected using IHC (score, 3) or FISH benefit most from trastuzumab-based therapy. Finally, the HER-2 protein is overexpressed in ovarian cancer, lung cancer, gastric cancer, and other solid tumors. However, the clinical significance of HER-2 overexpression in these tumors is not well defined.