We have reported that activation of the REarranged during Transfection (RET) receptor tyrosine kinase by its ligand GDNF decreases response of ER+ breast cancer cells to endocrine therapy, including AIs, and that the transcriptional signature of RET downstream signaling has both prognostic and predictive value in breast cancer [4, 11–13]. The gene discussed is ESR1; the disease is breast carcinoma.