Anti-estrogen treatment downregulated IGF-1R, IRS-1, and IRS-2 levels in ER+ breast cancer cells and human tumors (Figures 2C, 5C, Supplementary Figure 2A, Supplementary Figure 4, Supplementary Figure 5, Supplementary Figure 7C/7D), although effects varied between biological systems. This evidence concerns the gene IRS2 and breast carcinoma.