Role of HER3 expression and PTEN loss in patients with HER2-overexpressing metastatic breast cancer (MBC) who received taxane plus trastuzumab treatment

Br J Cancer. 2014 Jan 21;110(2):384-91. doi: 10.1038/bjc.2013.757. Epub 2013 Dec 17.

Abstract

Background: The aim of this study was to investigate the role of human epidermal growth factor receptor (HER3) and PTEN expression in patients with HER2-overexpressing metastatic breast cancer (MBC).

Methods: One hundred twenty-five MBC patients who were treated with taxane plus trastuzumab chemotherapy as first-line therapy were included in this analysis. Immunohistochemical (IHC) staining with HER3 and PTEN antibodies were conducted retrospectively.

Results: Patients who had negative HER3 staining (62.4%) had a better progression-free survival (PFS) than did those who had positive HER3 staining (P=0.001; median PFS, 21 vs 11 months). Patients who had a PTEN score >20 (78.1%) showed longer PFS than did those with a PTEN score ≤20 (P=0.006; median PFS, 13 vs 9 months). Patients who had a PTEN score >20 exhibited a longer overall survival (OS) than did those with a PTEN score ≤20 (P=0.005; median OS, 48 vs 25 months). HER3 negativity and PTEN loss were identified as independent risk factors for PFS. PTEN loss was identified as an independent risk factor for OS.

Conclusion: HER3 and PTEN expressions may be predictive markers, and PTEN expression may be a predictive and prognostic biomarker for trastuzumab treatment in HER2-positive MBCs.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics
  • Bridged-Ring Compounds / administration & dosage
  • Disease-Free Survival
  • Female
  • Humans
  • Middle Aged
  • PTEN Phosphohydrolase / deficiency*
  • PTEN Phosphohydrolase / genetics
  • Prognosis
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-3 / biosynthesis*
  • Receptor, ErbB-3 / genetics
  • Retrospective Studies
  • Taxoids / administration & dosage
  • Trastuzumab

Substances

  • Antibodies, Monoclonal, Humanized
  • Bridged-Ring Compounds
  • Taxoids
  • taxane
  • ERBB3 protein, human
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Trastuzumab