In in vitro cell and animal models of breast cancer, activation of RET signaling by GFLs enhances tumor cell proliferation, and survival and has been shown to promote estrogen-independent expression of a normally estrogen-ER-dependent transcriptional profile (Esseghir et al., 2007; Boulay et al., 2008; Plaza-Menacho et al., 2010; Wang C. et al., 2012; Gattelli et al., 2013, 2018). This evidence concerns the gene ESR1 and breast carcinoma.