Activated HER-receptors in predicting outcome of ER-positive breast cancer patients treated with adjuvant endocrine therapy

Breast. 2012 Oct;21(5):662-8. doi: 10.1016/j.breast.2012.07.005. Epub 2012 Jul 31.


The four human epidermal growth factor receptors (HER1-4) are involved in growth stimulation and may play a role in endocrine resistance. The receptors form dimers, leading to activation by mutual phosphorylation. Our purpose was to explore the role of the activated receptors (pHER1, pHER2, pHER3) in endocrine treated breast cancer in terms of co-expression and association with disease-free survival (DFS) in 1062 patients with ER-positive tumors. Furthermore, HER2 amplification was evaluated. We found positive associations between the phosphorylated receptors. pHER1 and pHER3 were co-expressed with one or two of the other activated receptors in 85% and 89% of tumors, respectively, whereas pHER2 was co-expressed with the other activated receptors in 54% of tumors. Except for HER2, which was associated with poor prognosis, none of the remaining markers were associated with DFS. However, frequent co-expression indicates a role of the other HER-family members in activation of HER2.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / surgery
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Double-Blind Method
  • ErbB Receptors / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Letrozole
  • Mastectomy*
  • Middle Aged
  • Nitriles / therapeutic use*
  • Phosphorylation
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, ErbB-2 / metabolism
  • Receptor, ErbB-3 / metabolism
  • Receptor, ErbB-4
  • Tamoxifen / therapeutic use*
  • Treatment Outcome
  • Triazoles / therapeutic use*


  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Nitriles
  • Triazoles
  • Tamoxifen
  • Letrozole
  • EGFR protein, human
  • ERBB2 protein, human
  • ERBB4 protein, human
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Receptor, ErbB-4