Free insulin-like growth factor-I and breast cancer risk

Int J Cancer. 2001 Mar 1;91(5):736-9. doi: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1111>;2-#.


Insulin-like growth factor-I (IGF-I) has mitogenic and anti-apoptotic effects on breast cancer cells. Epidemiologic studies have shown that high plasma levels of IGF-I and low levels of IGF binding protein (BP)-3 are associated with increased risk of breast cancer in premenopausal women. The actions of IGF-I are mediated through the IGF-I receptor (IGF-IR) and are regulated by IGFBPs. In circulation, most of the IGF-I binds to IGFBP-3, and binding of IGF-I to IGFBP-3 inhibits the actions of IGF-I. Since free IGF-I, which does not bind to IGFBPs, can readily cross the endothelial barrier to interact with IGF-IR, circulating free IGF-I is thought to be more relevant to the biologic activity of IGF-I. To examine the association of free IGF-I with breast cancer, we compared free IGF-I levels between 40 newly diagnosed breast cancer patients and 40 age- and race-matched healthy controls. Plasma levels of free IGF-I, total IGF-I and IGF-II, as well as total, intact and fragment IGFBP-3, were measured using commercial immunoassay kits. The association between IGF-I and breast cancer was examined using the conditional logistic regression analysis. Analysis of correlation (Spearman) showed that free IGF-I was correlated with total IGF-I and IGFBP-3 but not with IGF-II. The odds ratios for breast cancer patients having high plasma IGF-I (> or = median) after adjusting for menopausal status and IGFBP-3 were 2.00 (p < o r = 0.376) for total IGF-I and 6.31 (p < or = 0.047) for free IGF-I. A high ratio of IGF-I to IGFBP-3 was also associated with breast cancer (p < 0.05). No association was found for IGF-II, nor for total, intact and fragment IGFBP-3. The findings of this study suggest that measuring free IGF-I in circulation is more useful than measuring total IGF-I with respect to evaluation of an association between IGF-I and breast cancer risk.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age Factors
  • Breast Neoplasms / blood*
  • Breast Neoplasms / metabolism
  • Case-Control Studies
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor I / biosynthesis*
  • Insulin-Like Growth Factor II / biosynthesis
  • Middle Aged
  • Odds Ratio
  • Premenopause
  • Regression Analysis
  • Risk Factors


  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II