Further prospective trials are needed to investigate the potential clinical applications of ctDNA analysis in this setting of patients, but our results are in support of the hypothesis that ctDNAmutKRAS changes are associated with tumour dynamics, and that they may be used as a biomarker to predict who will take advantage from CDK4/6i, leading to personalized management in HR-positive/HER2-negative mBC patients, decreasing wastes of resources for the National Health System, and ensuring the best quality of life for patients. Here, ERBB2 is linked to neoplasm.