title: 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: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, 18-20 Waehringer Guertel, 1090, Vienna, Austria.
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Köstler
authors.forename: Gernot
authors.initials: G
authors.lastname: Hudelist
authors.forename: Werner
authors.initials: W
authors.lastname: Rabitsch
authors.forename: Klaus
authors.initials: K
authors.lastname: Czerwenka
authors.forename: Ruth
authors.initials: R
authors.lastname: Müller
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1; D000068878:Trastuzumab