IRS1 and breast cancer: These findings from human tumors collectively suggest that 1) ER drives the expression of IGF-1R, IRS-1, and IRS-2, and 2) IGF-1R/InsR kinase activity is required for feedback activation of PI3K/AKT upon inhibition of mTORC1, providing mechanistic insight into the effects of mTORC1 and ER inhibition on signaling in ER+ breast cancer.