Teysir Jimmitti, Lloyd Maxwell R, Alkassis Samer, Callahan Rena D, Fairley Ricki, Wander Seth A, Bardia Aditya, Jhaveri Komal L
Memorial Sloan Kettering Cancer Center, New York, NY.
Beth Israel Deaconess Medical Center, Boston, MA.
Am Soc Clin Oncol Educ Book. 2025 Jun;45(3):e473372. doi: 10.1200/EDBK-25-473372. Epub 2025 Jun 20.
CDK 4/6 inhibitors (CDK4/6i) remain part of the standard first-line treatment for patients with hormone receptor-positive metastatic breast cancer, offering demonstrable improvements in both progression-free survival and overall survival. However, resistance inevitably develops, and the optimal treatment sequencing after CDK4/6i progression remains undefined. Tumor heterogeneity and diverse resistance mechanisms-including alterations in and -complicate treatment decisions in the post-CDK4/6i setting. Genomic profiling has helped to characterize these and other clinically relevant alterations, uncovering new avenues for therapeutic intervention. Building on these insights, a growing number of novel endocrine agents, phosphoinositide-3-kinase/AKT pathway-targeted therapies, and antibody-drug conjugates (ADCs) have demonstrated efficacy in biomarker-selected populations and are reshaping the treatment landscape beyond CDK4/6i progression. This chapter reviews current standards of care, emerging therapeutic options, and evolving combination strategies across biomarker-defined subgroups. We also highlight how ongoing clinical trials and advances in molecular profiling are informing personalized approaches to overcome endocrine resistance and improve patient outcomes.
细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）仍然是激素受体阳性转移性乳腺癌患者标准一线治疗的一部分，在无进展生存期和总生存期方面都有显著改善。然而，耐药性不可避免地会出现，CDK4/6i进展后的最佳治疗顺序仍不明确。肿瘤异质性和多种耐药机制，包括[此处原文缺失相关内容]的改变，使CDK4/6i治疗后的治疗决策变得复杂。基因组分析有助于描述这些以及其他临床相关改变，为治疗干预开辟了新途径。基于这些见解，越来越多的新型内分泌药物、磷酸肌醇-3-激酶/AKT通路靶向疗法和抗体药物偶联物（ADC）在生物标志物选择的人群中显示出疗效，正在重塑CDK4/6i进展后的治疗格局。本章回顾了当前的护理标准、新兴的治疗选择以及生物标志物定义亚组中的联合治疗策略。我们还强调了正在进行的临床试验和分子分析的进展如何为克服内分泌耐药性和改善患者预后的个性化方法提供信息。
