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[新辅助乳腺癌的靶向治疗:细胞周期蛋白依赖性激酶4/6和聚(ADP-核糖)聚合酶抑制剂的作用]

[Targeted therapies in neoadjuvant breast cancer: The role of CDK4/6 and PARP inhibitors].

作者信息

Papazyan Thomas, Frénel Jean-Sébastien

机构信息

Institut de cancérologie de l'Ouest, 11, boulevard Jacques-Monod, 44800 St-Herblain, France.

Institut de cancérologie de l'Ouest, 11, boulevard Jacques-Monod, 44800 St-Herblain, France; Inserm, CRCI2NA, Nantes université, 44000 Nantes, France.

出版信息

Bull Cancer. 2025 Jul-Aug;112(7-8):757-770. doi: 10.1016/j.bulcan.2025.06.005. Epub 2025 Jul 16.

Abstract

Over the past decade, targeted therapies have significantly improved the prognosis of metastatic breast cancer. CDK4/6 and PARP inhibitors are now gaining traction in the adjuvant setting, and their potential use in the neoadjuvant context is also being explored. This review presents an analysis of the current scientific evidence and associated clinical perspectives. CDK4/6 inhibitors act on cell cycle dysregulation, commonly observed in hormone receptor-positive breast cancers. In the adjuvant setting, abemaciclib and ribociclib have shown improvements in progression-free survival (PFS) in the monarchE and NATALEE trials, respectively, leading to their approval by the European Medicines Agency. In the neoadjuvant context, although these agents have demonstrated a reduction in proliferation markers such as Ki67, their impact on clinical practice remains limited to date. PARP inhibitors are based on the concept of synthetic lethality, specifically targeting cancers with germline BRCA1 or BRCA2 mutations. In the adjuvant setting, the OlympiA trial demonstrated a significant improvement in both PFS and overall survival (OS). In the neoadjuvant setting, these agents have also shown effects on pathological markers, though the clinical relevance of these findings has yet to be clearly established. Overall, these results underscore the growing role of targeted therapies in the adjuvant management of breast cancer. The identification and validation of predictive biomarkers will be crucial in optimizing their use, both in adjuvant and neoadjuvant settings.

摘要

在过去十年中,靶向治疗显著改善了转移性乳腺癌的预后。细胞周期蛋白依赖性激酶4/6(CDK4/6)和聚(ADP-核糖)聚合酶(PARP)抑制剂目前在辅助治疗领域正逐渐受到关注,其在新辅助治疗中的潜在应用也在探索之中。本综述对当前的科学证据及相关临床观点进行了分析。CDK4/6抑制剂作用于激素受体阳性乳腺癌中常见的细胞周期失调。在辅助治疗中,阿贝西利和瑞博西利分别在monarchE和NATALEE试验中显示出无进展生存期(PFS)的改善,从而获得了欧洲药品管理局的批准。在新辅助治疗中,尽管这些药物已证明可降低增殖标志物如Ki67,但迄今为止它们对临床实践的影响仍然有限。PARP抑制剂基于合成致死的概念,专门针对具有种系BRCA1或BRCA2突变的癌症。在辅助治疗中,OlympiA试验显示PFS和总生存期(OS)均有显著改善。在新辅助治疗中,这些药物也对病理标志物显示出作用,不过这些发现的临床相关性尚未明确确立。总体而言,这些结果强调了靶向治疗在乳腺癌辅助治疗管理中日益重要的作用。预测生物标志物的识别和验证对于在辅助和新辅助治疗中优化其使用至关重要。

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