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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

Abstract

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.

Keywords

HER2 Overexpression Breast cancer Biologic therapy Antibody Hsp90 

Abbreviation

HER

Human epidermal growth factor receptor

Hsp

Heat shock protein

RTK

Receptor tyrosine kinase

ECD

Extracellular domain

PI3K

Phosphatidylinositol 3-kinase

MAPK

Mitogen-activated protein kinase

PLC

Phospholipase C

EGF

Epidermal growth factor

HB-EGF

Heparin binding EGF-like growth factor

PCR

Polymerase chain reaction

FISH

Fluoroscene in silu hybridization

MAb

Monoclonal antibody

ER

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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