Although CDK4/6 inhibitors play an important role in the treatment of breast cancer, studies have shown that a subset (10% to 20%) of hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2−) breast cancer patients are inherently insensitive to CDK4/6 inhibitors and that between 70% and 80% of CDK4/6 inhibitor-sensitive patients will develop refractory status after 12 to 36 months of treatment [10,11]. The gene discussed is CDK4; the disease is breast cancer.