ESR1 and breast cancer: The insulin-like growth factor binding proteins (IGFBP) are important regulators of the IGFR pathway, acting mainly by binding to the ligands IGF1, IGF2 and insulin, but they are also directly implicated in the process of carcinogenesis: IGFBP3 is involved in the regulation of DNA damage response [43] and IGFBPs 4 and 5 may prevent hormone-dependent activation of estrogen-receptor positive breast cancer cell growth in an IGF1R-independent manner [44].