Insulin-like Growth Factor Binding Proteins 1 and 3 and Breast Cancer Outcomes

Breast Cancer Res Treat. 2002 Jul;74(1):65-76. doi: 10.1023/a:1016075709022.

Abstract

The IGF family of growth factors is believed to play a role in the development and progression of breast cancer. We recently identified an adverse prognostic effect of insulin in breast cancer; we now report prognostic effects of circulating IGFBP's 1 and 3. 512 women with T1-3, N0-1, M0 breast cancer provided fasting blood which was analysed for IGFBP's I and 3. Information on body size, diet and traditional prognostic factors and treatment was obtained; women were followed for recurrence and death. IGFBP-1 levels correlated inversely with insulin levels (Spearman r = -0.60, p < 0.0001), reflecting known inhibition of IGFBP-1 gene expression by insulin. Insulin explained 36% of the variance in IGFBP-1 levels. IGFBP-1 levels were also correlated with obesity and diet. Levels of IGFBP-1 significantly predicted distant recurrence and death, hazard ratio (95% CI) for lower versus upper quartile 2.08 (1.20-3.61) and 3.0 (1.45-6.21), respectively. These effects persisted after adjustment for tumor-related variables and treatment but were not independent of insulin levels. High levels of IGFBP-3 predicted distant recurrence (hazard ratio upper v.s. lower quartile 1.8, 95% CI 1.1-3.0) but not death (hazard ratio 1.0, 95% CI 0.5-1.9). The effect on distant recurrence was restricted to postmenopausal women (hazard ratio 3.8, 95% CI 1.6-9.0) and to those with estrogen receptor positive tumors (p = 0.002). Prognostic effects of IGFBP-1 appear related to the known effect of insulin on IGFBP-1 gene expression. The adverse effect of IGFBP-3 on distant recurrence in postmenopausal women with estrogen receptor positive breast cancer should be further investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Body Mass Index
  • Breast Neoplasms / pathology*
  • Diet
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Insulin / pharmacology
  • Insulin-Like Growth Factor Binding Protein 1 / analysis*
  • Insulin-Like Growth Factor Binding Protein 1 / biosynthesis
  • Insulin-Like Growth Factor Binding Protein 3 / analysis*
  • Insulin-Like Growth Factor Binding Protein 3 / biosynthesis
  • Middle Aged
  • Neoplasm Metastasis*
  • Neoplasm Recurrence, Local*
  • Postmenopause
  • Predictive Value of Tests
  • Prognosis
  • Receptors, Estrogen
  • Survival

Substances

  • Insulin
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 3
  • Receptors, Estrogen