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

## TL;DR

This study finds that adding CDK 4/6 inhibitors to endocrine therapy in advanced breast cancer reduces the risk of central nervous system metastases and improves survival.

## Contribution

The study provides new evidence that CDK 4/6 inhibitors may reduce CNS metastasis risk in hormone receptor-positive, HER2-negative advanced breast cancer.

## Key findings

- CDKIs combined with endocrine therapy reduced CNS as the first metastatic site (3.7% vs. 9.5%).
- CNS metastasis-free survival was extended with CDKIs (71.6 months vs. 63.6 months).
- Overall CNS metastasis incidence was lower with CDKIs (7.9% vs. 15.5%).

## Abstract

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; p = 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%, p = 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.

Among 449 advanced HR+/HER2− breast cancer patients screened (August 2018–July 2022), 14 were excluded for CNS relapse. The remaining patients (n = 435) were allocated to either ET + CDKI (n = 215) or ET alone (n = 220), with subsequent comparative analysis of CNS metastasis incidence, CNSM‐FS, PFS, and OS.