Palbociclib is a highly specific, orally active CDK4/6 inhibitor currently approved for the treatment of hormone receptor-positive, HER2-negative (HR+/HER2neg) advanced breast cancer (BC) in combination with the endocrine agents letrozole or fulvestrant.1–3 Given the efficacy and the tolerability shown by CDK4/6 inhibitors, utilization of these drugs in clinical practice is common in patients with HR+/HER2neg advanced BC. This evidence concerns the gene ERBB2 and breast cancer.