Misawa et al., 2020 reported that the methylation of CALML5 led to its downregulation, and this showed a correlation with HPV-associated oropharyngeal cancer. Moreover, the ubiquitination of CALML5 in the nucleus was found to play a role in the carcinogenesis of breast cancer in premenopausal women (Debald et al., 2013). Our results suggested that the high expression of CALML5 in HER2+HR+ breast cancer patients may lead to the resistant of pyrotinib combined with tamoxifen and the introduction of dalpiciclib might overcome this drug resistance and offer better therapeutic effects. Here, CALML5 is linked to breast carcinoma.