The PALOMA 2 phase III trial demonstrated that in previously untreated patients with ER-positive, HER2-negative advanced breast cancer, the combination of palbociclib and letrozole resulted in a significantly longer progression-free survival compared with letrozole alone (24.8 versus 14.5 months, respectively, p < 0.001) [18]. This evidence concerns the gene ESR1 and breast carcinoma.