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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

Abstract

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.

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Acknowledgements

The authors gratefully acknowledge the assistance of Dr. Ernst Rücklinger for statistical analyses and Dr. Angelika Amanshauser for logistic support. In addition, we would like to thank the following collaborators who provided us histology samples (in alphabetical order): W. Adolf, H. Bankl, I. Brandl, H. Brustmann, J. Feichtinger, L. Gerstner, T. Kessler, M. Klimpfinger, K. Kofler, D. Kosak, S. Naude, W. Rausch, A. Soleiman, W. Ulrich, S. Wuketich.

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Correspondence to Wolfgang J. Köstler.

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Wolfgang J. Köstler and Gernot Hudelist equally contributed to this work.

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Köstler, W.J., Hudelist, G., Rabitsch, W. et al. 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 132, 9–18 (2006). https://doi.org/10.1007/s00432-005-0038-8

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Key words

  • Her-2/neu
  • Breast cancer
  • IGF-1R
  • Trastuzumab