The combination of cyclin D-dependent kinases 4 and 6 (CDK4/6) inhibitors (CDK4/6i) palbociclib, ribociclib and abemaciclib with endocrine therapy (ET) has been approved for the treatment of patients with advanced estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC)1–4. Here, ESR1 is linked to breast cancer.