The presence of activating mutations in KRAS and HRAS, as well as amplification in NRAS, have been identified in ER+/HER2-metastatic breast cancer cases exhibiting both intrinsic and acquired resistance for Abemaciclib (Wander et al., 2020) and Palbociclib (Haines et al., 2018; Sherr, 2018; Wander et al., 2020). The gene discussed is ESR1; the disease is breast cancer.