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

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 (≥median) after adjusting for menopausal status and IGFBP‐3 were 2.00 (p < = 0.376) for total IGF‐I and 6.31 (p < = 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. © 2001 Wiley‐Liss, Inc.