We identified the novel role of the dalpiciclib in HER2+/HR+ breast cancer, provided evidence that CALML5 may serve as a potential risk factor in the treatment of HER2+HR+ breast cancer and the introduction of dalpiciclib might overcome the drug resistance to pyrotinib + tamoxifen due to the expression of CALML5 in HER2+HR+ breast cancer. This evidence concerns the gene CALML5 and breast cancer.