ESR1 and breast cancer: Recently, inhibitors such as palbociclib, ribociclib and abemaciclib [34] that target CDK4/6 have shown significant clinical efficacy in metastatic ER + BC by prolonging progression-free survival when given in combination with either the AI letrozole as first-line therapy in endocrine sensitive BC [11, 12], or with the selective ER downregulator Fulv, as second-line therapy in endocrine resistant disease [13].