Basic research identifying the role of the cyclin D-CDK4/6-Rb axis in G1 to S cell cycle transit, followed by translational and clinical studies in which this axis was linked to breast cancer progression and antiestrogen resistance (46, 47), culminated in the development of CDKi’s currently used in combination with endocrine treatments for ER+ HER2 negative breast cancer (48). This evidence concerns the gene ESR1 and breast carcinoma.