Associations of insulin-like growth factor and insulin-like growth factor binding protein-3 with mortality in women with breast cancer

Int J Cancer. 2013 Mar 1;132(5):1191-200. doi: 10.1002/ijc.27753. Epub 2012 Sep 1.

Abstract

Elevated circulating insulin-like growth factor-1 (IGF-1), a breast epithelial cell mitogen, is associated with breast cancer development. However, its association with breast cancer survival is not established. Circulating concentrations of IGF-1 are controlled via binding proteins, including IGF Binding Protein-3 (IGFBP-3), that may modulate the association of IGF-1 with breast-cancer outcomes. We measured IGF-1 and IGFBP-3 concentrations in serum from 600 women enrolled in the health, eating, activity, and lifestyle (HEAL) study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer. We evaluated the association between IGF-1 and IGFBP-3, and as a ratio, modeled using quintile cut-points, with risk of breast cancer-specific (n = 42 deaths) and all-cause mortality (n = 87 deaths) using Cox proportional hazards models. In models adjusted for body mass index, ethnicity, tamoxifen use at time of blood draw, treatment received at diagnosis and IGFBP-3, women in the highest quintile of IGF-1 level had an increased risk of all-cause mortality (Hazard Ratio (HR) = 3.10, 95% CI 1.21-7.93, p = 0.02), although no dose-response association was evident. The IGF-1/IGFBP-3 ratio, an indicator of free IGF-I levels, was significantly associated with increasing risk of all-cause mortality (HR = 2.83, 95% CI 1.25-6.36 p(trend) = 0.01, upper vs. lower quintile) in a fully adjusted model. In conclusion, high serum levels of IGF-1 and the IGF-1/IGFBP-3 ratio were associated with increased risk of all-cause mortality in women with breast cancer. These results need to be confirmed in larger breast cancer survivor cohorts.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Body Mass Index
  • Breast Neoplasms / blood*
  • Breast Neoplasms / mortality*
  • California / epidemiology
  • Cohort Studies
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / blood*
  • Insulin-Like Growth Factor I / metabolism*
  • Middle Aged
  • New Mexico / epidemiology
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • SEER Program
  • Washington / epidemiology

Substances

  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I