Cyclin-dependent kinase (CDK) 4/6 inhibition in combination with endocrine therapy is the standard-of-care treatment for patients with advanced-stage hormone receptor-positive, HER2 non-amplified (HR⁺HER2⁻) breast cancer. These agents can also be administered as adjuvant therapy to patients with higher-risk early stage disease. Nonetheless, the clinical success of these agents has created several challenges, such as how to address acquired resistance, identifying which patients are most likely to benefit from therapy prior to treatment, and understanding the optimal timing of administration and sequencing of these agents. In this Review, we describe the rationale for targeting CDK4/6 in patients with breast cancer, including a summary of updated clinical evidence and how this should inform clinical practice. We also discuss ongoing research efforts that are attempting to address the various challenges created by the widespread implementation of these agents.

细胞周期蛋白依赖性激酶 (CDK) 4/6 抑制与内分泌治疗相结合是晚期激素受体阳性、HER2 非扩增 (HR ⁺ HER2 ⁻ ) 乳腺癌患者的标准治疗方法。这些药物也可以作为辅助治疗用于患有高风险早期疾病的患者。尽管如此，这些药物的临床成功带来了一些挑战，例如如何解决获得性耐药、在治疗前确定哪些患者最有可能从治疗中受益，以及了解这些药物的最佳给药时机和顺序。在这篇综述中，我们描述了乳腺癌患者靶向 CDK4/6 的基本原理，包括更新的临床证据的总结以及这应如何为临床实践提供信息。我们还讨论了正在进行的研究工作，这些研究工作试图解决这些药物的广泛实施所带来的各种挑战。