Insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), and mammographic breast density

Abstract

9501 Background: A few small studies have suggested that higher IGF-I and lower IGFBP-3 may be associated with increased premenopausal mammographic breast density, one of the strongest known breast cancer risk factors. This large cross-sectional study was designed specifically to evaluate the associations of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 molar ratio with breast density. Methods: For this study, 784 premenopausal and 791 postmenopausal healthy women were recruited during screening mammography examinations. Using a computer-assisted method, a single observer assessed mammographic breast density with high reproducibility (intraclass correlation coefficient = 0.98). Blood samples collected at the time of the mammography allowed measurement of plasma IGF-I and IGFBP-3 levels by ELISA methods (coefficients of variation below 10% and 13%, respectively). Spearman's partial correlation coefficients (r) were used to evaluate the associations while adjusting for confounding factors including age, body mass index and IGF-I or IGFBP-3 when applicable. Results: Among premenopausal women, breast density is positively associated with IGF-I and IGF-I/IGFBP-3 ratio (r = 0.084, p = 0.019 and r = 0.070, p = 0.051, respectively) and negatively associated with IGFBP-3 (r = −0.123, p = 0.0005). No significant correlations were observed among postmenopausal women. Correlations among postmenopausal women (p-values) for IGF-I, IGFBP-3 and their ratio were 0.038 (0.282), −0.019 (0.593) and 0.035 (0.332), respectively. Conclusions: To date, this is the largest study of the relation of IGF to breast density. IGF-I and the IGF-I/IGFBP-3 ratio were correlated with mammographic breast density among premenopausal women supporting the view that the IGF axis plays a role in the development of some breast cancers among premenopausal women by its influence on breast density. No significant financial relationships to disclose.