ESR1 and breast carcinoma: Estradiol (E2) and its receptor ER enhance the expression and activation of the IGF-1R41, 42 tumorigenic signaling cascade including upregulation of IRS-1 resulting in enhanced phosphatidylinositol 3′-kinase (PI3K) pathways.43 Therefore, it was believed that treating breast cancer with dual targeting of ER and IGF-1R could improve clinical benefit compared with targeting ER alone.