The standard first line therapy for patients with metastatic (m), hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer (BC) is the combination therapy of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors with endocrine therapy (ET)1–5 which has positively affected progression-free survival (PFS) when compared to ET alone6–9 and is even beneficial in patients with clinically aggressive disease compared to chemotherapy10. This evidence concerns the gene NR4A1 and breast cancer.