Prognostic significance of IGF-1R expression in patients treated with breast-conserving surgery and radiation therapy

Radiother Oncol. 2010 Aug;96(2):204-8. doi: 10.1016/j.radonc.2010.03.009. Epub 2010 Mar 24.

Abstract

Background: Insulin-like growth factor (IGF) receptor is a key receptor in apoptotic protection, cell adhesion, longevity, and transformation into a cancerous cell and can induce malignant changes in the presence of the IGF ligand. Over-expression of IGF-1R has been associated with resistance to radiation. Inhibitors of IGF-1R have been shown to enhance tumor radiation sensitivity and amplify radiation therapy-induced apoptosis. The purpose of this study is to evaluate the prognostic significance of IGF-1R expression in patients with breast cancer treated with breast conserving therapy.

Materials and methods: Paraffin specimens from 345 women with early stage breast cancer treated with BCT were constructed into tissue microarrays and stained for IGF-1R, COX-2 and p53. The molecular profiles were correlated with clinical-pathologic factors, overall, local, and distant relapse-free survival. The association between IGF-1R, other co-variables, and outcome was assessed.

Results: IGF-1R over-expression was identified in 197 cases (57%). IGF-1R over-expression was found to be correlated with African-American race (p=0.0233), p53 status (p=0.0082) and COX-2 expression (p<0.0001). While IGF-1R over-expression was associated with lower overall survival (p=0.0224) in node-negative patients, there was no impact of IGF-1R expression on local control.

Conclusions: In node-negative patients, patients with high levels of IGF-1R were found to have a significant reduction in overall survival, but no apparent effect on local control. Given the limited published data on IGF-1R in early stage, conservatively treated patients, further studies investigating IGF-1R expression in this cohort are necessary.

MeSH terms

  • Age of Onset
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / radiotherapy*
  • Breast Neoplasms / surgery*
  • Chemotherapy, Adjuvant
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Mastectomy, Segmental*
  • Microarray Analysis
  • Middle Aged
  • Neoplasm Staging / methods
  • Outcome Assessment, Health Care
  • Prognosis
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism*
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Receptor, IGF Type 1