ImportancePoly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors have revolutionized the treatment of patients with germline BRCA1/2-associated breast cancer, representing the first targeted therapy capable of improving outcomes in patients with hereditary tumors. However, resistance to PARP inhibitors occurs in almost all patients.ObservationsThis narrative review summarizes the biological rationale behind the use of PARP inhibitors in breast cancer, as well as the available evidence, recent progress, and potential future applications of these agents. Recent studies have shown that the benefit of PARP inhibitors extends beyond patients with germline BRCA1/2-associated metastatic breast cancer to patients with somatic BRCA1/2 variants and to those with germline PALB2 alterations. Moreover, these agents proved to be effective both in the metastatic and adjuvant settings. However, patients with metastatic breast cancer usually do not achieve the long-term benefit from PARP inhibitors observed in other tumor types. Mechanisms of resistance have been identified, but how to effectively target them is largely unknown. Ongoing research is investigating both novel therapeutics and new combination strategies to overcome resistance. PARP1-selective inhibitors, by sparing the hematological toxic effects induced by the PARP2 blockade, are promising agents to be combined with chemotherapy, antibody-drug conjugates, and other targeted therapies.Conclusions and RelevanceAlthough the efficacy of PARP inhibitors is well established, many questions persist. Future research should focus on identifying predictive biomarkers and therapeutic strategies to overcome resistance. Integrating well-designed translational efforts into all clinical studies is thereby crucial to laying the groundwork for future insights from ongoing research.

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用于乳腺癌治疗的 PARP 抑制剂

重要性聚（腺苷二磷酸核糖）聚合酶（PARP）抑制剂彻底改变了种系患者的治疗乳腺癌1/2相关乳腺癌，代表第一种能够改善遗传性肿瘤患者预后的靶向治疗。然而，几乎所有患者都会对 PARP 抑制剂产生耐药性。观察这篇叙述性综述总结了在乳腺癌中使用 PARP 抑制剂的生物学原理，以及这些药物的现有证据、最新进展和潜在的未来应用。最近的研究表明，PARP 抑制剂的益处不仅限于生殖系患者乳腺癌1/2- 与躯体相关的转移性乳腺癌患者乳腺癌1/2变异体和具有种系的变异体PALB2变更。此外，这些药物被证明在转移和辅助治疗中均有效。然而，转移性乳腺癌患者通常无法从其他肿瘤类型中观察到的 PARP 抑制剂中获得长期获益。耐药机制已被确定，但如何有效地针对它们尚不清楚。正在进行的研究正在研究克服耐药性的新疗法和新组合策略。 PARP1 选择性抑制剂可避免 PARP2 阻断引起的血液毒性作用，是与化疗、抗体药物偶联物和其他靶向治疗相结合的有前途的药物。结论和相关性尽管 PARP 抑制剂的疗效已得到充分证实，但仍有许多问题坚持。未来的研究应侧重于识别预测生物​​标志物和克服耐药性的治疗策略。因此，将精心设计的转化工作整合到所有临床研究中对于为正在进行的研究的未来见解奠定基础至关重要。