ESR1 and breast cancer: Palbociclib (PD0332991) is the first oral CDK4/6 inhibitor with a simultaneous use of letrozole as first-line therapy, resulting in the significantly improved median PFS in advanced breast cancer with ER positive and HER2 negative (24.8 vs 14.5 months [PALOMA2]) as well as with Fulvestrant in endocrine pretreated patients (9.2 vs 3.8 months [PALOMA-3])70, 71.