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种系致病性变异无癌携带者管理中的争议与开放性问题

Controversies and Open Questions in Management of Cancer-Free Carriers of Germline Pathogenic Variants in .

作者信息

Bernstein-Molho Rinat, Friedman Eitan, Evron Ella

机构信息

The Oncogenetics Unit, Chaim Sheba Medical Center, Tel-Hashomer, The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 5265601, Israel.

Assuta Medical Center, Tel-Aviv, Israel, The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 8436322, Israel.

出版信息

Cancers (Basel). 2022 Sep 22;14(19):4592. doi: 10.3390/cancers14194592.

Abstract

Females harboring germline BRCA1/BRCA2 (BRCA) P/LPV are offered a tight surveillance scheme from the age of 25−30 years, aimed at early detection of specific cancer types, in addition to risk-reducing strategies. Multiple national and international surveillance guidelines have been published and updated over the last two decades from geographically diverse countries. We searched for guidelines published between 1 January 2015 and 1 May 2022. Differences between guidelines on issues such as primary prevention, mammography screening in young (<30 years) carriers, MRI screening in carriers above age 65 years, breast imaging (if any) after risk-reducing bilateral mastectomy, during pregnancy, and breastfeeding, and hormone-replacement therapy, are just a few notable examples. Beyond formal guidelines, BRCA carriers’ concerns also focus on the timing of risk-reducing surgeries, fertility preservation, management of menopausal symptoms in cancer survivors, and pancreatic cancer surveillance, issues that, for some, there are no data to support evidence-based recommendations. This review discusses these unsettled issues, emphasizing the importance of future studies to enable global guideline harmonization for optimal surveillance strategies. Moreover, it raises the unmet need for personalized risk stratification and surveillance in BRCA P/LPV carriers.

摘要

携带种系BRCA1/BRCA2(BRCA)致病性/可能致病性变异(P/LPV)的女性从25至30岁起就会接受严密的监测方案,除了采取降低风险的策略外,该方案旨在早期发现特定癌症类型。在过去二十年里,来自不同地理区域的多个国家和国际监测指南已经发布并更新。我们检索了2015年1月1日至2022年5月1日期间发布的指南。指南之间在诸如一级预防、对年轻(<30岁)携带者进行乳腺钼靶筛查、对65岁以上携带者进行MRI筛查、双侧预防性乳房切除术后(如有)、孕期及哺乳期的乳房成像以及激素替代疗法等问题上存在差异,这些只是几个显著的例子。除了正式的指南外,BRCA携带者关注的问题还集中在降低风险手术的时机、生育力保留、癌症幸存者更年期症状的管理以及胰腺癌监测等方面,对于其中一些问题,目前尚无数据支持循证推荐。本综述讨论了这些未解决的问题,强调了未来研究对于实现全球指南协调以制定最佳监测策略的重要性。此外,它还提出了BRCA P/LPV携带者对个性化风险分层和监测的未满足需求。

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