Insulin-like growth factor receptor (IGF-1R) in breast cancer subtypes

Breast Cancer Res Treat. 2012 Feb;132(1):131-42. doi: 10.1007/s10549-011-1529-8. Epub 2011 May 15.

Abstract

Insulin-like growth factor-1 receptor (IGF-1R) is expressed in normal and malignant breast tissue and has been implicated in cell survival and resistance to cytotoxic therapies. We sought to assess the prognostic impact of IGF-1R expression among patients with early breast cancer and among breast cancer subtypes. Patients with stages I-III breast cancer with archival tumor tissue were included. Paraffin tissue blocks were used to construct a tissue microarray that was stained for ER, PR, Ki-67, HER2, EGFR, and cytokeratins 5/6 to classify the breast subgroups and for expression of IGF-1R, p27, and Bcl2 by immunohistochemistry. Kaplan-Meier plots were created by subtypes. Associations between IGF-1R and prognostic variables were examined in multivariate analysis. Among 2,871 eligible women the prognostic cut point for IGF-1R expression for breast-cancer-specific survival (BCSS) was Allred score < 7 versus ≥ 7. IGF-1R was ≥ 7 in 52% (LuminalA), 57.5% (LuminalB), 44.8% (LuminalHER2), 9.7% HER2-enriched, and 22.5% (Basal-like), P = 1.3 × 10(-52). IGF-1R+ was associated with age ≥ 50, lower histopathology grade, ER+, HER2 negativity (-), high p27 and high Bcl2 score. IGF-1R ≥ 7 was associated with better BCSS among LuminalB patients, hazard ratio = 0.64 (0.49-0.84); P = 1.2 × 10(-3,) and worse outcome in the HER2-enriched subtype, hazard ratio = 2.37 (1.21-4.64); P = 0.012. IGF-1R correlates with good prognostic markers among patients with early breast cancer and is differentially expressed with variable prognostic impact among breast cancer subtypes. Results may have relevance to the development of therapeutics targeting IGF-1R.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Case-Control Studies
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Female
  • Gene Expression
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism*
  • Tumor Burden

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2
  • Cyclin-Dependent Kinase Inhibitor p27
  • Receptor, IGF Type 1