CDK4/6 inhibitors in combination with endocrine therapy have become the standard of care in HR-positive/HER2-negative advanced breast cancer and have provided strong clinical evidence of improved disease control over the past decade[6][4]. These agents (palbociclib, ribociclib, abemaciclib) block the cyclin D-CDK4/6 complex, leading to blocked phosphorylation of the Rb protein and cell cycle arrest in the G1 phase, thereby suppressing tumor cell growth[1][4]. Clinical trials have demonstrated a statistically significant prolongation of progression-free survival (PFS) when CDK4/6 inhibition is added to hormonal therapy compared to hormonal therapy alone[4]. Some studies (e.g., in the neoadjuvant setting) have shown a more significant reduction in proliferation with the combination of iCDK4/6 plus ET than with ET alone, and a "rebound" phenomenon has also been observed after treatment[1]. After the development of endocrine resistance, the cyclin D-CDK4/6 complex remains a key target, and CDK4/6 inhibitors may reverse or delay the emergence of resistance[2][4]. Various large studies (MONARCH, MONALEESA, PALOMA) provide efficacy data in subgroups including patients with hormone resistance; results vary between studies due to different design and stratification of patients[5]. Understanding the molecular mechanisms of resistance and optimizing subsequent sequencing of therapies remains a major challenge, which is the subject of further research[6].