We hypothesized that genetic variation in IGF signaling will modify risk of breast cancer in women carrying deleterious mutations in BRCA1 and BRCA2. In the present study, we focused on investigating the association of variants in IGF1, IGFBP1, IGFBP2, IGFBP5, IGF1R, and IRS1 as potential disease modifiers in mutation carriers of BRCA1 and BRCA2. Here, IRS1 is linked to breast cancer.