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BRCA1 和 BRCA2 种系致病性变异的乳腺癌患者治疗领域中的聚腺苷二磷酸核糖聚合酶抑制剂:意大利共识文件和批判性评价。

Parp-inhibitors in the therapeutic landscape of breast cancer patients with BRCA1 and BRCA2 pathogenic germline variants: An Italian consensus paper and critical review.

机构信息

Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy; Humanitas Clinical and Research Center-IRCCS, Humanitas Cancer Center, Via Manzoni 56, 20089 Rozzano, Milan, Italy.

Department of Oncology and Hematology, University Hospital of Modena, via del Pozzo 71, 41124 Modena, Italy.

出版信息

Cancer Treat Rev. 2024 Nov;130:102815. doi: 10.1016/j.ctrv.2024.102815. Epub 2024 Aug 21.

DOI:10.1016/j.ctrv.2024.102815
PMID:39208751
Abstract

The introduction of PARP inhibitors has revolutionized the management and treatment of patients with pathogenic germline variants of BRCA1/2 who have developed breast cancer. The implementation of PARP inhibitors in clinical settings can be challenging due to their overlapping indications with other drugs, including both recently approved medications and those with proven efficacy. This study utilized the Delphi method to present the first Italian consensus regarding genetic testing, the use of PARP inhibitors in both early and metastatic settings, and strategies for managing the potential toxicity of these novel drugs. The Panel unanimously agreed on various issues, including the timing, techniques, and patient characteristics for BRCA1/2 genetic testing, andthe appropriate placement of PARP inhibitors in the treatment algorithm for both early and advanced breast cancer. Nevertheless, some areas of divergence became evident, particularly regarding the use of axillary surgery for therapeutic purposes and the application of hormone replacement therapy in cases of bilateral mastectomy and risk-reducing salpingo-oophorectomy for patients treated for triple negative breast cancer. Additional research is needed in these particular domains to improve the care of patients with breast cancer who bear an increased genetic risk.

摘要

PARP 抑制剂的引入彻底改变了携带 BRCA1/2 种系致病性变异的乳腺癌患者的治疗管理方式。由于 PARP 抑制剂与其他药物(包括最近批准的药物和已证明有效的药物)的适应证重叠,因此在临床实践中实施 PARP 抑制剂可能具有挑战性。本研究采用德尔菲法,就遗传检测、PARP 抑制剂在早期和转移性环境中的应用以及这些新型药物潜在毒性的管理策略提出了意大利首个共识。专家组一致同意了包括 BRCA1/2 遗传检测的时机、技术和患者特征,以及在早期和晚期乳腺癌治疗算法中适当放置 PARP 抑制剂等各种问题。然而,一些分歧点变得明显,特别是关于用于治疗目的的腋窝手术的应用以及在双侧乳房切除术和风险降低的输卵管卵巢切除术的情况下应用激素替代疗法,这些都是为治疗三阴性乳腺癌而接受治疗的患者。在这些特定领域需要进一步研究,以改善具有遗传风险增加的乳腺癌患者的护理。

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