In multiple experimental systems, including primary mammary tumors, cultured human cells, and Brca1-deficient mice, Shukla and colleagues showed that BRCA1 deficiency resulted in increased expression of insulin-like growth factor receptor substrate 1 (IRS1), insulin-like growth factor-1 receptor (IGF1R), IGFBP2, and increased levels of serum IGF1 [19]. Here, IRS1 is linked to breast cancer.