Prognostic value of HER3, PTEN and p-HER2 expression in patients with HER2positive breast cancer

Postepy Hig Med Dosw (Online). 2015 May 5:69:586-97. doi: 10.5604/17322693.1151339.

Abstract

Background: HER2 overexpression is an unfavorable prognostic factor in patients with breast cancer, but it is also a target for the monoclonal antibody trastuzumab, which is effective in adjuvant and palliative settings. HER2 positivity is an inclusion criterion for immunotherapy, but it is not a positive predictive factor, and only half of patients benefit from the treatment.

Aim: The aim of this study was to evaluate the prognostic and predictive value of HER3, PTEN and phosphorylated HER2 (p-HER2) expression in primary breast tumors of patients treated with trastuzumab in an adjuvant or palliative regimen.

Material/methods: Immunohistochemical (IHC) analysis with 3 antibodies specific to the proteins was performed in tumor specimens obtained from 81 HER2-positive patients treated with trastuzumab.

Results: HER3 overexpression was present in 55.6% of the examined tumors, and PTEN or pHER2 positivity was present in 32.0% and 34.6% of them, respectively. HER3 overexpression and PTEN positivity correlated with larger tumor size (p=0.016 and p=0.008, respectively). p-HER2 positivity correlated with more advanced clinical stage of the disease (p=0.032). There was no correlation between the proteins' expression and survival for 31 patients treated with trastuzumab in the palliative regimen.

Discussion: HER3 overexpression, PTEN positivity and p-HER2 positivity in tumor cells of HER2-positive patients correlate with more advanced clinical stage of breast cancer. Expression of these proteins does not predict outcome of trastuzumab treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • PTEN Phosphohydrolase / genetics*
  • Phosphorylation
  • Prognosis
  • Receptor, ErbB-2 / drug effects
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Receptor, ErbB-3 / genetics*
  • Trastuzumab / therapeutic use*
  • Treatment Outcome

Substances

  • ERBB2 protein, human
  • ERBB3 protein, human
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Trastuzumab