Palbociclib (Ibrance, PD-0332991), the first CDK4/6 inhibitor synthesized and tested in clinical trials, is currently indicated in combination with ET both as first- and second-line therapeutic option in patients with ER+/HER2− breast cancer [5] and is under investigation for the treatment of patients with ER+/HER2+ disease. Here, ESR1 is linked to breast cancer.