Besides, in the recent MUKDEN 01 clinical trial (NCT04486911), the combination use of pyrotinib (anti-HER2 drug), letrozole (endocrine drug), and dalpiciclib (CDK4/6 inhibitor) exerted optimal therapeutic effect in HER2+HR+ breast cancer patients and offered novel chemo-free neoadjuvant therapy for the treatment of HER2+HR+ breast cancer (Niu et al., 2022), yet the underlying mechanism warrants further investigation. The gene discussed is CDK4; the disease is breast cancer.