In the initial Phase II (PALOMA-1) and III (PALOMA-2-and -3) trials, palbociclib in combination with fulvestrant or letrozole demonstrated superior efficacy for advanced ER+ breast cancer compared to either antiestrogen used as a single agent treatment, with a doubling of progression-free survival (41, 42); increased median progression-free survival (PFS) of up to 27.6 months for letrozole + palbociclib compared to 14.5 months for letrozole as a single agent. The gene discussed is ESR1; the disease is breast cancer.