ESR1 and breast cancer: Indeed, IIGFs is implicated in tumor progression and metastasis of both ER-positive and ER-negative BC cells (Bartella et al., 2012; De Marco et al., 2015) and frequently shows features of deregulation such as (i) overexpression and activation of IGF-1R, IR, and IR/IGF-1R hybrids in malignant cells, (ii) dysregulated expression and/or bioavailability of IGF-1 and IGF-2 in both malignant and stromal cells, and (iii) increased IR-A:IR-B ratio and establishment of IR-A/IGF2 autocrine/paracrine loops (Malaguarnera et al., 2012a).