It has been shown that IGF-1R activation in breast cancer results in the tyrosine phosphorylation of IRS-1/2 and Src-homology-2-domains.94 These molecules are believed to be part of multiple additional tumorigenic adapter proteins and molecules such as Shc, Gab, Crk, and PI3K,95 which are recruited by IGF-1R network receptors. This evidence concerns the gene PIK3CA and breast cancer.