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The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine Ross JS; Slodkowska EA; Symmans WF; Pusztai L; Ravdin PM; Hortobagyi GNOncologist 2009[Apr]; 14 (4): 320-68The human epidermal growth factor receptor (HER-2) oncogene encodes a transmembrane tyrosine kinase receptor that has evolved as a major classifier of invasive breast cancer and target of therapy for the disease. The validation of the general prognostic significance of HER-2 gene amplification and protein overexpression in the absence of anti-HER-2 targeted therapy is discussed in a study of 107 published studies involving 39,730 patients, which produced an overall HER-2-positive rate of 22.2% and a mean relative risk for overall survival (OS) of 2.74. The issue of HER-2 status in primary versus metastatic breast cancer is considered along with a section on the features of metastatic HER-2-positive disease. The major marketed slide-based HER-2 testing approaches, immunohistochemistry, fluorescence in situ hybridization, and chromogenic in situ hybridization, are presented and contrasted in detail against the background of the published American Society of Clinical Oncology-College of American Pathologists guidelines for HER-2 testing. Testing issues, such as the impact of chromosome 17 polysomy and local versus central HER-2 testing, are also discussed. Emerging novel HER-2 testing techniques, including mRNA-based testing by real-time polymerase chain reaction and DNA microarray methods, HER-2 receptor dimerization, phosphorylated HER-2 receptors, and HER-2 status in circulating tumor cells, are also considered. A series of biomarkers potentially associated with resistance to trastuzumab is discussed with emphasis on the phosphatase and tensin homologue deleted on chromosome ten/Akt and insulin-like growth factor receptor pathways. The efficacy results for the more recently approved small molecule HER-1/HER-2 kinase inhibitor lapatinib are also presented along with a more limited review of markers of resistance for this agent. Additional topics in this section include combinations of both anti-HER-2 targeted therapies together as well as with novel agents including bevacizumab, everolimus, and tenespimycin. A series of novel HER-2-targeting agents is also presented, including pertuzumab, ertumaxomab, HER-2 vaccines, and recently discovered tyrosine kinase inhibitors. Biomarkers predictive of HER-2 targeted therapy toxicity are included, and the review concludes with a consideration of HER-2 status in the prediction of response to non-HER-2 targeted treatments including hormonal therapy, anthracyclines, and taxanes.|Anthracyclines/administration & dosage[MESH]|Antibodies, Monoclonal, Humanized[MESH]|Antibodies, Monoclonal/administration & dosage[MESH]|Antineoplastic Combined Chemotherapy Protocols/*therapeutic use[MESH]|Bevacizumab[MESH]|Biomarkers, Tumor/*analysis[MESH]|Breast Neoplasms/*chemistry/*drug therapy/mortality/pathology[MESH]|Everolimus[MESH]|Evidence-Based Medicine[MESH]|Female[MESH]|Gene Expression Regulation, Neoplastic/drug effects[MESH]|Humans[MESH]|Immunohistochemistry[MESH]|In Situ Hybridization[MESH]|Lapatinib[MESH]|Neoplasm Staging[MESH]|Polymerase Chain Reaction[MESH]|Practice Guidelines as Topic[MESH]|Prognosis[MESH]|Pyrazoles/administration & dosage[MESH]|Pyrimidines/administration & dosage[MESH]|Quinazolines/administration & dosage[MESH]|RNA, Messenger/analysis[MESH]|Receptor, ErbB-2/*analysis/*drug effects[MESH]|Sirolimus/administration & dosage/analogs & derivatives[MESH]|Survival Analysis[MESH]|Taxoids/administration & dosage[MESH]|Trastuzumab[MESH]|Treatment Outcome[MESH]|Up-Regulation/drug effects[MESH] |
