Insulin-like growth factor-1 receptor (IGF-1R) expression does not predict for resistance to trastuzumab-based treatment in patients with Her-2/neu overexpressing metastatic breast cancer

J Cancer Res Clin Oncol. 2006 Jan;132(1):9-18. doi: 10.1007/s00432-005-0038-8. Epub 2005 Sep 24.


Purpose: Her-2/neu and the insulin-like growth factor-1 receptor (IGF-1R) share common postreceptor-signaling pathways, and pre-clinical models have implicated IGF-1R-signaling in resistance to treatment with the anti-Her-2/neu antibody trastuzumab. The present analysis was performed to evaluate the clinical relevance of IGF-1R expression within the context of trastuzumab-based therapy.

Patients and methods: We performed immunohistochemical (IHC) analysis for IGF-1R expression in tumor specimens from 72 patients receiving trastuzumab-based treatment for Her-2/neu-overexpressing metastatic breast cancer at a single institution. IGF-1R status was evaluated using different cut-offs for positivity regarding staining intensity and staining pattern. IGF-1R positivity was then correlated with clinical patient and biological tumor characteristics and the clinical course of disease of patients under trastuzumab-based therapy.

Results: No pattern or intensity of staining for IGF-1R correlated with any of the clinical or biological characteristics. Likewise, response, clinical benefit, progression-free and overall survival were independent of IGF-1R expression in both, univariate and multivariate analyses (all P>0.05).

Conclusions: We conclude that IGF-1R expression is not a major predictor of the clinical efficacy of trastuzumab-based treatment in patients with Her-2/neu- overexpressing metastatic breast cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Disease-Free Survival
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Predictive Value of Tests
  • Receptor, ErbB-2 / metabolism*
  • Receptor, IGF Type 1 / metabolism*
  • Survival Analysis
  • Trastuzumab
  • Treatment Outcome
  • Up-Regulation


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Receptor, ErbB-2
  • Receptor, IGF Type 1
  • Trastuzumab