ESR1 and breast cancer: On the other hand, a subsequent randomized phase II clinical trial called PALOMA-1/TRIO-18 showed that the combination of letrozole with palbociclib showed a remarkable improvement in the median PFS of 20.2 months compared to 10.2 months with letrozole alone (HR, 0.49, p = 0.0004) in ER-positive HER2-negative BC patients receiving this treatment as first-line therapy [42].