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

IF 11.3 1区 化学 Q1 CHEMISTRY, PHYSICAL ACS Catalysis Pub Date : 2024-08-21 DOI:10.1016/j.ctrv.2024.102815
Alberto Zambelli , Laura Cortesi , Mariangela Gaudio , Grazia Arpino , Giampaolo Bianchini , Francesco Caruso , Saverio Cinieri , Giuseppe Curigliano , Lucia Del Mastro , Sabino De Placido , Alessandra Fabi , Lucio Fortunato , Daniele Generali , Alessandra Gennari , Stefania Gori , Giovanni Grandi , Valentina Guarneri , Marco Klinger , Lorenzo Livi , Caterina Marchiò , Michelino De Laurentiis
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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, and the 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.

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Parp抑制剂在BRCA1和BRCA2致病基因变异乳腺癌患者治疗中的应用:意大利共识文件和评论
PARP 抑制剂的问世彻底改变了对 BRCA1/2 基因变异患者的管理和治疗。由于 PARP 抑制剂的适应症与其他药物(包括新近获批的药物和已被证实具有疗效的药物)重叠,因此在临床环境中实施 PARP 抑制剂具有挑战性。本研究采用德尔菲法,首次就基因检测、PARP 抑制剂在早期和转移性病例中的使用以及管理这些新型药物潜在毒性的策略达成了意大利共识。专家小组在多个问题上达成了一致意见,包括 BRCA1/2 基因检测的时机、技术和患者特征,以及 PARP 抑制剂在早期和晚期乳腺癌治疗方案中的适当位置。尽管如此,一些领域的分歧也很明显,特别是在使用腋窝手术治疗方面,以及在双侧乳房切除术和三阴性乳腺癌患者降低风险的输卵管切除术中应用激素替代疗法方面。需要在这些特定领域开展更多研究,以改善对遗传风险增加的乳腺癌患者的护理。
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来源期刊
ACS Catalysis
ACS Catalysis CHEMISTRY, PHYSICAL-
CiteScore
20.80
自引率
6.20%
发文量
1253
审稿时长
1.5 months
期刊介绍: ACS Catalysis is an esteemed journal that publishes original research in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. It offers broad coverage across diverse areas such as life sciences, organometallics and synthesis, photochemistry and electrochemistry, drug discovery and synthesis, materials science, environmental protection, polymer discovery and synthesis, and energy and fuels. The scope of the journal is to showcase innovative work in various aspects of catalysis. This includes new reactions and novel synthetic approaches utilizing known catalysts, the discovery or modification of new catalysts, elucidation of catalytic mechanisms through cutting-edge investigations, practical enhancements of existing processes, as well as conceptual advances in the field. Contributions to ACS Catalysis can encompass both experimental and theoretical research focused on catalytic molecules, macromolecules, and materials that exhibit catalytic turnover.
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