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HER2 activation results from heterodimerization with another ERBB member or by homodimerization when HER2 concentration are high, for instance in cancer. [8] Amplification or over-expression of this oncogene has been shown to play an important role in the development and progression of certain aggressive types of breast cancer.
Another receptor that often plays a role in breast cancer, although it is not a hormone receptor, is the human epidermal growth factor receptor 2 (HER2). The overexpression of HER2 is determined by immunohistochemistry (IHC), or with fluorescent in situ hybridization in those equivocal cases where IHC does not provide a clear result.
ErbB2 overexpression can occur in breast, ovarian, bladder, non-small-cell lung carcinoma, as well as several other tumor types. [28] Trastuzumab or Herceptin inhibits downstream signal cascades by selectively binding to the extracellular domain of ErbB-2 receptors to inhibit it. [ 28 ]
Approval was based on KATHERINE (NCT01772472 [25]), a randomized, multicenter, open-label trial of 1486 patients with HER2-positive EBC. [24] Breast tumor samples were required to demonstrate HER2 overexpression defined as 3+ IHC or ISH amplification ratio ≥ 2.0 determined at a central laboratory using Ventana's PATHWAY anti-HER2-/neu (4B5 ...
The HER2 gene product is over-expressed in SkBr3 cells SkBr3 cells were derived from a pleural effusion due to an adenocarcinoma originating in a 43-year-old caucasian female. [ 1 ] The cell line over-expresses the HER2 gene product, which has been implicated in several breast cancer proliferation pathways.
In early-stage HER2-positive breast cancer, trastuzumab-containing regimens improved overall survival (Hazard ratio (HR) = 0.66) and disease-free survival (HR = 0.60). [38] Increased risk of heart failure (RR = 5.11) and decline in left ventricular ejection fraction ( relative risk RR = 1.83) were seen in these trials as well. [ 38 ]
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