Breast Cancer

, Volume 8, Issue 1, pp 45–51 | Cite as

Biological and clinical significance of her2 overexpression in Breast Cancer

  • Junichi Kurebayashi
Review Article


The product of the HER2/neu proto-oncogene, HER2, is the second member of the human epidermal growth factor receptor (HER) family of tyrosine kinase receptors and has been suggested to be a ligand orphan receptor. Ligand-dependent heterodimerization between HER2 and another HER family member, HER1, HER3 or HERA, activates the HER2 signaling pathway. The intracellular signaling pathway of HER2 is thought to involve ras-MAPK, MAPK-independent S6 kinase and phospholipase C-γ signaling pathways. However, the biological consequences of the activation of these pathways are not yet completely known.

Amplification of the HER2 gene and overexpression of the HER2 protein induces cell transformation and has been demonstrated in 10% to 40% of human breast cancer. HER2 overexpression has been suggested to associate with tumor aggressiveness, prognosis and responsiveness to hormonal and cytotoxic agents in breast cancer patients. These findings indicate that HER2 is an appropriate target for tumor-specific therapies. A number of approaches have been investigated: (1) a humanized monoclonal antibody against HER2, rhuMAbHE/?2 (trastuzumab), which is already approved for clinical use in the treatment of patients with metastatic breast cancer; (2) tyrosine kinase inhibitors, such as emodin, which block HER2 phosphorylation and its intracellular signaling; (3) active immunotherapy, such as vaccination; and (4) heat shock protein (Hsp) 90-associated signal inhibitors, such as radicicol derivatives, which induce degradation of tyrosine kinase receptors, such as HER2.


HER2 Overexpression Breast cancer Biologic therapy Antibody Hsp90 



Human epidermal growth factor receptor


Heat shock protein


Receptor tyrosine kinase


Extracellular domain


Phosphatidylinositol 3-kinase


Mitogen-activated protein kinase


Phospholipase C


Epidermal growth factor


Heparin binding EGF-like growth factor


Polymerase chain reaction


Fluoroscene in silu hybridization


Monoclonal antibody


Estrogen receptor


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Copyright information

© The Japanese Breast Cancer Society 2001

Authors and Affiliations

  • Junichi Kurebayashi
    • 1
  1. 1.Department of Breast and Thyroid SurgeryKawasaki Medical SchoolJapan

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