Incidence of Metastasis in the Central Nervous System in Advanced Breast Cancer Treated With CDK 4/6 Inhibitors: A Multicenter, Retrospective Study

Central nervous system (CNS) metastasis remains a major cause of mortality in advanced breast cancer (ABC). While cyclin-dependent kinase 4/6 inhibitors (CDKIs) combined with endocrine therapy (ET) delay resistance in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative ABC, their impact on CNS metastasis development has not been fully elucidated. This retrospective study analyzed 435 ABC patients without baseline CNS metastases who received first-line ET with or without CDKIs across three Chinese hospitals (August 2018-July 2022). Primary end points included CNS as the first metastatic site, CNS metastasis-free survival (CNSM-FS), and CNS metastasis incidence over time. Secondary end points were progression-free survival (PFS) and overall survival (OS). The results indicated that the addition of CDKIs to ET significantly reduced the incidence of CNS as the first site of metastasis (3.7% vs. 9.5% with ET alone; <i>p</i> = 0.0015) and extended CNSM-FS (71.6 months vs. 63.6 months, respectively; hazard ratio [HR], 0.53; 95% CI, 0.31-0.92). Overall, CNS metastasis incidence was lower with ET + CDKIs (7.9% vs. 15.5%, <i>p</i> = 0.014), and improvements were observed in both PFS and OS. These findings suggest that ET + CDKIs as first-line therapy in ABC may reduce CNS metastasis risk and extend CNSM-FS, offering a potential strategy for preventing CNS metastases.