The ability of nuclear FoxO3a to restore the sensitivity of breast cancer cell to tamoxifen is finally highlighted by the down regulation of several proteins involved in GF signals, e.g., components of the PI3K/AKT pathway, the major inhibitor of FoxO3a activity, two adaptor proteins IRS1 and SHC1 and the transduction factor RAF1. This evidence concerns the gene IRS1 and breast cancer.