Palbociclib, ribociclib and abemaciclib have demonstrated statistically significant and clinically meaningful PFS benefit when added to ET in both the first and second-line advanced ER+/HER2-breast cancer settings (Cristofanilli et al., 2016; Finn et al., 2016; Sledge et al., 2017; Hortobagyi et al., 2018; Slamon et al., 2018; Johnston et al., 2019). The gene discussed is ESR1; the disease is breast cancer.