Abstract
Human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive factor in breast cancer. HER2 is overexpressed in approximately 15%–20% of invasive breast carcinomas and is associated with earlier recurrence, shortened disease free survival, and poor prognosis. Trastuzumab (Herceptin) a “humanized” monoclonal antibody targets the extracellular domain of HER2 and is widely used in the management of HER2 positive breast cancers. Accurate assessment of HER2 is thus critical in the management of breast cancer. The aim of this paper is to present a comprehensive review of HER2 with reference to its discovery and biology, clinical significance, prognostic value, targeted therapy, current and new testing modalities, and the interpretation guidelines and pitfalls.
Highlights
Introduction andHuman epidermal growth factor receptor 2 (HER2) BiologyIn 1981, Shih et al discovered novel transmissible genes which caused transformation of NIH 3T3 cells upon transfection of DNA obtained from rat neuroblastomas [1]
The results indicated that patients with high HER2 expression (≥50%) who received high-dose chemotherapy had a significantly longer disease-free survival and overall survival as compared to the patients with no or low HER2 expression (
37% of the patients achieved minimal responses or stable disease. These results were confirmed by larger multinational clinical trial involving 222 women with HER2-positive metastatic breast carcinoma that had progressed after chemotherapy
Summary
In 1981, Shih et al discovered novel transmissible genes which caused transformation of NIH 3T3 cells upon transfection of DNA obtained from rat neuroblastomas [1]. The same group identified a 185,000 Dalton phosphoprotein obtained from the sera of young mice injected with secondary transfectants containing neuroblastoma transforming sequence [2]. This neu oncogene was later identified in genomes of fetal rat neuro/glioblastomas cell lines derived from tumors induced by ethylnitrosurea [3]. The nucleic acid sequence of the neu gene was homologous to the erb-B oncogene and the neu-associated tumor antigen p-185 was antigenically related but distinct from the epidermal growth factor (EGF) receptor. Pathology Research International mice, overexpression of HER2 led to development of mammary tumors and induction of metastatic disease [18,19,20]
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