Background: Breast cancer (BC) incidence increases with age, particularly in HR-positive/HER2-negative subtypes. Cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6is) alongside endocrine therapy (ET) have emerged as promising treatments for HR-positive/HER2-negative advanced and early BC. However, their efficacy, safety, and impact on quality of life (QoL) in older and frail patients remain underexplored. Methods: This position paper assesses the existing literature from 2015 to 2024, focusing on CDK4/6is use in patients aged 65 years and older with HR-positive/HER2-negative BC. Results: Our analysis methodically addresses critical questions regarding the utilization of CDK4/6is in the elderly BC patient population, organizing findings from the metastatic and adjuvant settings. In the metastatic setting, CDK4/6is significantly improve progression-free survival (PFS), paralleling benefits observed in younger patients, and suggest potential overall survival (OS) benefits, warranting further investigation. Despite an increased incidence of grade ≥ 3 adverse events (AEs), such as neutropenia and asthenia, CDK4/6is present a markedly lower toxicity profile compared to traditional chemotherapy, with manageable side effects. QoL analysis indicates that integrating CDK4/6is into treatment regimens does not significantly impact elderly BC patients’ daily life and symptom management. Special attention is given to frail subgroups, and personalized approaches are recommended to balance efficacy and adverse effects, such as starting with ET alone and introducing CDK4/6is upon progression in patients with a low disease burden. Transitioning to the adjuvant setting, early results, particularly with abemaciclib, indicate positive effects on disease-free survival (DFS), emphasizing the need for continued analysis to validate these findings and assess long-term implications. However, data on older patients are insufficient to conclude whether they truly benefit from this treatment. Conclusion: Overall, CDK4/6is present a favorable benefit-risk profile in older BC patients, at least in advanced BC; however, further research is warranted to optimize treatment strategies and improve outcomes in this population
背景：乳腺癌（BC）发病率随年龄增长而上升，尤其在激素受体阳性/人表皮生长因子受体2阴性亚型中。细胞周期蛋白依赖性激酶4和6抑制剂（CDK4/6is）联合内分泌治疗（ET）已成为激素受体阳性/人表皮生长因子受体2阴性晚期及早期乳腺癌的有效治疗策略。然而，其在老年及衰弱患者中的疗效、安全性及对生活质量（QoL）的影响仍需深入探讨。方法：本立场文件评估了2015年至2024年的现有文献，重点关注CDK4/6is在65岁及以上激素受体阳性/人表皮生长因子受体2阴性乳腺癌患者中的应用。结果：我们的分析系统探讨了CDK4/6is在老年乳腺癌患者群体中应用的关键问题，分别从转移性和辅助治疗两个场景整合研究结果。在转移性场景中，CDK4/6is显著改善无进展生存期（PFS），其获益与年轻患者相当，并提示潜在的总生存期（OS）获益，值得进一步研究。尽管≥3级不良事件（AEs）（如中性粒细胞减少和乏力）发生率有所增加，但与传统化疗相比，CDK4/6is的毒性特征显著降低，且副作用可控。生活质量分析表明，将CDK4/6is纳入治疗方案不会显著影响老年乳腺癌患者的日常生活和症状管理。特别关注衰弱亚组，建议采用个体化治疗策略以平衡疗效与不良反应，例如对疾病负荷较低的患者可先单独使用内分泌治疗，待疾病进展时再引入CDK4/6is。在辅助治疗场景中，早期结果（特别是阿贝西利）显示对无病生存期（DFS）具有积极影响，强调需要持续分析以验证这些发现并评估长期影响。然而，关于老年患者的数据尚不足以确定他们是否真正从该治疗中获益。结论：总体而言，CDK4/6is在老年乳腺癌患者中展现出良好的获益-风险特征（至少在晚期乳腺癌中）；然而，仍需进一步研究以优化该人群的治疗策略并改善临床结局。
肿瘤(癌症)患者之家