Expression of the HER1-4 family of receptor tyrosine kinases in breast cancer

J Pathol. 2003 Jul;200(3):290-7. doi: 10.1002/path.1370.


EGFr/HER1 and c-erbB-2/HER2 expression are associated with poor prognosis in breast cancer. The type I receptor tyrosine kinase (RTK) family to which they belong has four members (HER1-4). In this study, expression of HER1-4 and oestrogen receptor (ER) expression were determined by immunohistochemistry in 220 breast carcinomas. Elevated expression of HER1 was observed in 16.4%, HER2 in 22.8%, HER3 in 17.5%, and HER4 in 11.9% of these tumours. Patients whose tumours overexpressed HER1, 2 or 3 had reduced survival (p= <0.001), whereas those whose tumours overexpressed HER4 had increased survival (p=0.013); 38.6% of cases overexpressed one or more of HER1, 2 or 3. HER4 was rarely overexpressed with other HERs (1.4% of cases). Cox's multiple regression analysis demonstrated that overexpression of HER1/2/3, HER4, and standard prognostic indicators independently affected survival. HER1-3 expression was related to ER negativity (p<0.0001, chi2). Patients with ER-positive, HER1-3-positive tumours had a significantly poorer survival (p<0.001) than those with ER-positive/HER-negative or HER4-positive tumours. Expression of HER RTKs displays complex interactions between different family members. There is a strong interaction, in terms of survival, between HER expression and ER expression. The development of HER-targeted agents (eg Herceptin, Iressa), and agents targeted at the downstream signalling pathways, therefore provides new possibilities in the treatment of breast cancer.

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • ErbB Receptors / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, erbB / genetics*
  • Genes, erbB-1 / genetics
  • Genes, erbB-2
  • Humans
  • Immunohistochemistry / methods
  • Prognosis
  • Protein-Tyrosine Kinases / genetics*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-3 / genetics
  • Receptor, ErbB-4
  • Receptors, Estrogen / analysis


  • Receptors, Estrogen
  • ERBB4 protein, human
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Receptor, ErbB-4