Estradiol also reflects an interesting example of how we interpret the role of IGFBP2 in cancer, as previously described, IGFBP2 is generally considered to be oncogenic in breast cancer; however, IGFBP2 expression, in vivo, is induced by estradiol in normal breast tissue (98), whereas in the rat mammary adenocarcinoma, R3230AC, IGFBP2 expression is reduced following E2 treatment (99). Here, IGFBP2 is linked to cancer.