Dysregulated cellular proliferation represents a hallmark feature across all cancers. Aberrant activation of the cyclin-dependent kinase 4 and 6 (CDK4/6) pathway, independent of mitogenic signaling, engenders uncontrolled breast cancer cell proliferation. Consequently, the advent of CDK4/6 inhibition has constituted a pivotal milestone in the realm of targeted breast cancer therapy. The combination of CDK4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) has emerged as the foremost therapeutic modality for patients afflicted with hormone receptor-positive (HR + )/HER2-negative (HER2-) advanced breast cancer. At present, the Food and Drug Administration (FDA) has sanctioned various CDK4/6i for employment as the primary treatment regimen in HR + /HER2- breast cancer. This therapeutic approach has demonstrated a substantial extension of progression-free survival (PFS), often amounting to several months, when administered alongside endocrine therapy. Within this comprehensive review, we systematically evaluate the utilization strategies of CDK4/6i across various subpopulations of breast cancer and explore potential therapeutic avenues following disease progression during application of CDK4/6i therapy.

细胞增殖失调是所有癌症的一个标志性特征。细胞周期蛋白依赖性激酶 4 和 6 (CDK4/6) 通路的异常激活（与有丝分裂信号传导无关）会导致乳腺癌细胞增殖失控。因此，CDK4/6 抑制的出现已成为乳腺癌靶向治疗领域的一个关键里程碑。CDK4/6 抑制剂 (CDK4/6i) 与内分泌治疗 (ET) 的组合已成为治疗激素受体阳性 (HR + )/HER2 阴性 (HER2-) 晚期乳腺癌患者的最重要的治疗方式。目前，美国食品药品监督管理局（FDA）已批准多种CDK4/6i作为HR+/HER2-乳腺癌的主要治疗方案。这种治疗方法与内分泌治疗一起使用时，已证明无进展生存期 (PFS) 显着延长，通常可达几个月。在这篇综合综述中，我们系统地评估了 CDK4/6i 在乳腺癌不同亚群中的利用策略，并探索了 CDK4/6i 治疗应用过程中疾病进展后的潜在治疗途径。