Wen Yan-Ling, Bi Xi-Wen, Zhang Xue-Wen, Wang Si-Fen, Jiang Chang, Wang Li, Zhong Yong-Yi, Huang Yuan-Yuan, Zhao Jian-Li, Chen Qian-Jun, Xue Cong, Yuan Zhong-Yu
Department of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Provincial Clinical Research Center for Cancer Sun Yat-sen University Cancer Center Guangzhou China.
Department of Anesthesiology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Provincial Clinical Research Center for Cancer Sun Yat-sen University Cancer Center Guangzhou China.
MedComm (2020). 2025 May 24;6(6):e70221. doi: 10.1002/mco2.70221. eCollection 2025 Jun.
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; = 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%, = 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.
中枢神经系统（CNS）转移仍然是晚期乳腺癌（ABC）患者死亡的主要原因。虽然细胞周期蛋白依赖性激酶4/6抑制剂（CDKIs）联合内分泌治疗（ET）可延缓激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性ABC患者的耐药性，但它们对CNS转移发展的影响尚未完全阐明。这项回顾性研究分析了435例无基线CNS转移的ABC患者，这些患者在三家中国医院（2018年8月至2022年7月）接受了一线ET治疗，部分患者联合使用了CDKIs。主要终点包括以CNS作为首个转移部位、CNS无转移生存期（CNSM-FS）以及随时间推移的CNS转移发生率。次要终点为无进展生存期（PFS）和总生存期（OS）。结果表明，ET联合CDKIs显著降低了以CNS作为首个转移部位的发生率（分别为3.7%和9.5%；单独使用ET时；P = 0.0015），并延长了CNSM-FS（分别为71.6个月和63.6个月；风险比[HR]，0.53；95%可信区间[CI]，0.31 - 0.92）。总体而言，ET + CDKIs组的CNS转移发生率较低（分别为7.9%和15.5%，P = 0.014），且PFS和OS均有改善。这些发现表明，ET + CDKIs作为ABC的一线治疗方案可能降低CNS转移风险并延长CNSM-FS，为预防CNS转移提供了一种潜在策略。
