These findings led to the design and implementation of PALOMA (Palbociclib: Ongoing Trials in the Management of BC)–1, a randomized, study designed to evaluate [palbociclib + letrozole] vs. letrozole alone as first-line therapy in post-menopausal women with ER+/HER2− advanced BC [87,88]. This evidence concerns the gene ESR1 and breast cancer.