Background: Identifying patients with gBRCAm is crucial to facilitate screening strategies, preventive measures and the usage of targeted therapeutics in their management. This review examines the evidence for the latest predictive and therapeutic approaches inBRCA-associated cancers. Clinical Description: Data supports the use of adjuvant olaparib in patients with gBRCAm high-risk HER2-negative breast cancer. In advanced gBRCAm HER2-negative breast cancer, the PARPis talazoparib and olaparib have demonstrated benefit over standard chemotherapy. In ovarian cancer, olaparib, niraparib or rucaparib can be used as monotherapy in frontline maintenance. Olaparib and bevacizumab as a combination can also be used as frontline maintenance. In the relapsed platinum-sensitive setting, olaparib, niraparib and rucaparib are effective maintenance options inBRCAm patients who are PARPi naive. Both olaparib and rucaparib are effective options inBRCAm metastatic castrate-resistant prostate cancer (mCRPC). Evidence also exists for the benefit of PARPi combinations in mCRPC. In metastatic pancreatic cancer, olaparib can be used in gBRCAm patients who are responding to platinum chemotherapy. However, there may be a development of PARPi resistance. Understanding the pathophysiology that contributes to such resistance may allow the development of novel therapeutics. Combination therapy appears to have promising results in emerging trials. Seeking avenues for subsidised genetic testing can reduce the total costs of cancer management, leading to improve detection rates. Conclusion: Identifying breast, ovarian, pancreatic and prostate cancer patients with gBRCAm plays a crucial predictive role in selecting those who will benefit significantly from PARPi therapy. The use of PARPi in gBRCAm HBOC-related cancers has resulted in significant survival benefits. BeyondBRCA1/2, HRR gene assessment and the consideration of other cancer predisposition syndromes may allow more patients to be eligible for and benefit from targeted therapies.
背景：识别携带胚系BRCA基因突变（gBRCAm）的患者对于在其管理中促进筛查策略、采取预防措施以及应用靶向治疗至关重要。本综述探讨了BRCA相关癌症最新预测与治疗方法的相关证据。临床描述：数据显示，对于携带gBRCAm的高风险HER2阴性乳腺癌患者，辅助使用奥拉帕利具有临床价值。在晚期gBRCAm HER2阴性乳腺癌中，PARP抑制剂他拉唑帕利和奥拉帕利已显示出优于标准化疗的获益。在卵巢癌中，奥拉帕利、尼拉帕利或卢卡帕利可作为一线维持治疗的单药使用。奥拉帕利与贝伐珠单抗联合方案也可用于一线维持治疗。在复发性铂敏感情况下，对于未使用过PARP抑制剂的BRCAm患者，奥拉帕利、尼拉帕利和卢卡帕利均是有效的维持治疗选择。在BRCAm转移性去势抵抗性前列腺癌（mCRPC）中，奥拉帕利和卢卡帕利均为有效治疗选择。现有证据也表明PARP抑制剂联合疗法在mCRPC中具有获益。在转移性胰腺癌中，奥拉帕利可用于对铂类化疗有反应的gBRCAm患者。然而，PARP抑制剂耐药性可能发生。理解导致此类耐药的病理生理机制可能有助于开发新型治疗方法。联合疗法在正在进行的临床试验中显示出前景。寻求基因检测补贴途径可降低癌症管理的总成本，从而提高检出率。结论：识别携带gBRCAm的乳腺癌、卵巢癌、胰腺癌和前列腺癌患者，对于筛选出能从PARP抑制剂治疗中显著获益的人群具有关键的预测作用。在gBRCAm相关的遗传性乳腺癌卵巢癌综合征（HBOC）相关癌症中使用PARP抑制剂已带来显著的生存获益。除BRCA1/2外，同源重组修复（HRR）基因评估及其他癌症易感综合征的考量，可能使更多患者有资格接受靶向治疗并从中获益。
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