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Introduction  Levels of insulin-like growth factor (IGF)-I and its main binding protein (IGFBP-3) have been associated with breast cancer risk among premenopausal women. However, associations of IGFBP-3 levels with breast cancer risk have been inconsistent, possibly due to the different predominant forms of circulating IGFBP-3 (intact versus fragmented) that were measured in these studies. Here, we examine the association of breast cancer risk factors with intact and total IGFBP-3 levels.    Methods  This cross-sectional study includes 737 premenopausal women recruited at screening mammography. Plasma intact and total IGFBP-3 and IGF-I levels were measured by enzyme-linked immunosorbent assay methods. Percent and absolute breast density were estimated using a computer-assisted method. The associations were evaluated using generalized linear models and Pearson (r) or Spearman (r s ) partial correlation coefficients.    Results  Means ± standard deviations of intact and total IGFBP-3 levels (ng/mL) were 1,044 ± 234 and 4,806 ± 910, respectively. Intact and total IGFBP-3 levels were correlated with age and smoking. Levels of intact IGFBP-3 were negatively correlated with waist-to-hip ratio (WHR) (r = -0.128;  P  = 0.0005), parity (r s  = -0.078;  P  = 0.04), and alcohol intake (r = -0.137;  P  = 0.0002) and positively correlated with energy intake (r = 0.075;  P  = 0.04). In contrast, total IGFBP-3 levels were positively correlated with WHR (r = 0.115;  P  = 0.002), parity (r s  = 0.089;  P  = 0.02), body mass index (BMI) (r = 0.115;  P  = 0.002), physical activity (r = 0.118;  P  = 0.002), and IGF-I levels (r = 0.588;  P  < 0.0001) and negatively correlated with percent or absolute breast density (r = -0.095;  P  = 0.01 and r = -0.075;  P  = 0.04, respectively).    Conclusion  Our data show that associations of some breast cancer risk factors with intact levels of IGFBP-3 are different from those with total (intact and fragmented) IGFBP-3 levels. These findings suggest that different molecular forms of IGFBP-3 may bear different relations to premenopausal breast cancer risk.

Intact and total insulin-like growth factor-binding protein-3 (IGFBP-3) levels in relation to breast cancer risk factors: a cross-sectional study