ESR1 and breast carcinoma: In 2015, palbociclib became the first CDK4/6 inhibitor to be approved by the FDA and was granted accelerated approval in combination with the nonsteroidal aromatase inhibitor letrozole as first-line therapy for treating advanced ER+HER2- breast cancer following results from the Phase II PALOMA-1 study (NCT00721409), which showed that the addition of palbociclib to letrozole therapy in advanced ER+HER2- breast cancer nearly doubled progression free survival from 10.2 months to 20.2 months[56,57].