使用多聚(ADP-核糖)聚合酶抑制剂治疗 BRCA 基因突变乳腺癌患者的实际数据

Evelyn Lilian Beas-Lozano, H. Verduzco-Aguirre, Roberto Gonzalez-Salazar, Y. Chávarri-Guerra
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摘要

乳腺癌是全球最常见的癌症类型。遗传性乳腺癌占新发病例的 10%,4%-5% 的病例与 BRCA1 或 BRCA2 基因的致病变异有关。近年来,多聚腺苷-二磷酸核糖聚合酶抑制剂(PARPi)奥拉帕利(olaparib)和他拉唑帕利(talazoparib)被批准用于治疗 BRCA 相关、HER2 阴性乳腺癌患者。根据OlympiAD、OlympiA和EMBRACA三期试验的结果,这些药物在早期和晚期治疗中取得了积极的疗效,毒性反应良好。然而,这些随机试验中的患者都是经过严格筛选的,因此常规临床治疗中患者的毒性和疗效令人担忧。自奥拉帕利和他拉唑帕利被批准用于治疗晚期人表皮生长因子受体2阴性(HER2阴性)乳腺癌以来,一些IIIb-IV期试验、扩大入组和回顾性入组提供了这些疗法在注册试验中代表性不足的患者亚群中的疗效和耐受性信息,如老年人、表现状态不佳的患者和重度预处理患者。本综述旨在对现实世界中乳腺癌患者使用 PARPi 的相关信息进行批判性回顾。
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Real-world data in patients with BRCA mutated breast cancer treated with poly (ADP-ribose) polymerase inhibitors
Breast cancer is the most common type of cancer globally. Hereditary breast cancer accounts for 10% of new cases and 4%–5% of cases are associated to pathogenic variants in BRCA1 or BRCA2 genes. In recent years, poly-adenosine-diphosphate-ribose polymerase inhibitors (PARPi) olaparib and talazoparib have been approved for patients with BRCA -associated, HER2 -negative breast cancer. These drugs have shown positive results in the early and advanced setting with a favourable toxicity profile based on the OlympiAD, OlympiA and EMBRACA phase 3 trials. However, patients included in these randomised trials are highly selected, making toxicity and efficacy in patients encountered in routine clinical care a concern. Since the approval of olaparib and talazoparib for advanced human epidermal growth factor receptor 2-negative (HER2-negative) breast cancer, several phase IIIb–IV trials, expanded access cohorts, and retrospective cohorts have provided information on the efficacy and tolerability of these treatments in patient subgroups underrepresented in the registration trials, such as older adults, patients with poor performance status, and heavily pretreated patients. The aim of this review is to present a critical review of the information regarding the use of PARPi in real-world breast cancer patients.
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