The potent antiproliferative effect of CDK4/6 inhibition in ER+ breast cancer was demonstrated by tumor Ki-67 analysis in serial biopsies in the NeoPalAna trial (a phase II trial of anastrozole and palbociclib, a CDK4/6 inhibitor, in women with clinical stage II-III ER+/HER2− breast cancer), in which the addition of palbociclib to anastrozole induced complete cell cycle arrest (Ki-67 ≤ 2.7%) in 87% of patients, as compared with 26% following single-agent anastrozole treatment [19]. Here, ESR1 is linked to breast cancer.