The analysis of the heterogeneity from the Whole Exome Sequencing of tumor samples according to the sensitivity/resistance status revealed an increased heterogeneity as measured by subclonal dominance in ribociclib-resistant compared to sensitive patients (Fig. 3A, the other heterogeneity meaures are reported in Supplementary Fig. 7), while no difference was observed in sensitive/resistant patients treated with letrozole, suggesting that heterogeneity might contribute to acquired resistance, specific to CDK4/6i. This evidence concerns the gene CDK4 and neoplasm.