The PALOMA-2 trial, designed to confirm the findings of the PALOMA-1 trial, was a randomized (2:1), multicenter, double-blind study evaluating palbociclib in combination with letrozole vs. letrozole plus placebo as a first-line treatment for postmenopausal patients with ER+, HER2– advanced breast cancer (ClinicalTrials.gov, 2015a). Here, ESR1 is linked to breast carcinoma.