Immunoblot further verified that neratinib effectively downregulated Cyclin D1, CDK4 and EGFR by inhibiting the HER2 pathway, thus enhancing the efficacy of CDK4/6 inhibitor combined with endocrine therapy in HR+/HER2-low breast cancer (P < 0.01) (Fig. 5G). This evidence concerns the gene CDK4 and breast cancer.