Circulating levels of IGF-1 have been found to be positively associated with breast cancer risk.6–9 A pooled analysis of 17 prospective studies found that the association of circulating IGF-1 with breast cancer was not modified by circulating levels of IGF-binding protein 3 (IGFBP-3) (i.e., the major protein carrier of IGF-1 in circulation), and seems to be specific to estrogen-positive tumors.10 This evidence concerns the gene IGFBP3 and breast cancer.