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遗传风险评估与预防的最新进展:基因检测面板在乳腺癌中的作用。

An update on genetic risk assessment and prevention: the role of genetic testing panels in breast cancer.

机构信息

Familial Breast Cancer Clinic, Mount Sinai Hospital , Toronto , ON , Canada.

Department of Molecular Genetics, University of Toronto , Toronto , Canada.

出版信息

Expert Rev Anticancer Ther. 2019 Sep;19(9):787-801. doi: 10.1080/14737140.2019.1659730. Epub 2019 Sep 7.

Abstract

: In the past 5 years, multi-gene panels have replaced the practice of and genetic testing in cases of suspected inherited breast cancer susceptibility. A variety of genes have been included on these panels without certainty of their clinical utility. Pertinent current and historical literature was reviewed to provide an up-to-date snapshot of the changing landscape of the use of gene panel tests in the context of breast cancer. : Following a recent review of the evidence, 10 genes have been found to have definitive evidence of increased breast cancer risk with variable penetrance. Here, we review the recent changes to the practice of multi-gene panel use in breast cancer diagnoses, including an update on next generation sequencing, alternative models of genetic testing, considerations when ordering these panel tests, and recommendations for management in identified carriers for a variety of genes. A comparison of screening recommendations and carrier frequencies from recent studies is also explored. Lastly, we consider what the future of hereditary oncologic genetic testing holds. : The transition to multi-gene panels in breast cancer patients has improved the likelihood of capturing a rare variant in a well-established gene associated with hereditary breast cancer (e.g. ). There is also an increase in the likelihood of uncovering an uncertain result. This could be in the form of a variant of uncertain significance, or a pathogenic variant in a gene with questionable breast cancer risk-association. Concurrently, a changing landscape of who orders genetic tests will improve access to genetic testing. This pervasiveness of genetic testing must be accompanied with increased genetic literacy in all health-care providers, and access to support from genetics professionals for management of patients and at-risk family members.

摘要

在过去的 5 年中,多基因面板已经取代了疑似遗传性乳腺癌易感性病例中的 和 基因检测。这些面板上包含了各种基因,但并不能确定其临床效用。我们回顾了当前和历史相关文献,以提供一个最新的视角来了解基因面板检测在乳腺癌中的应用变化情况。

在最近对证据进行审查后,发现 10 个基因具有明确的增加乳腺癌风险的证据,但其外显率存在差异。在这里,我们回顾了多基因面板在乳腺癌诊断中的使用实践的最新变化,包括下一代测序的更新、遗传测试的替代模型、订购这些面板测试时的考虑因素,以及针对各种基因的携带者的管理建议。我们还探讨了近期研究中筛查建议和携带者频率的比较。最后,我们考虑遗传性肿瘤遗传检测的未来前景。

多基因面板在乳腺癌患者中的应用转变提高了在与遗传性乳腺癌相关的既定基因中捕获罕见变异的可能性(例如 )。同时,也增加了发现不确定结果的可能性。这可能表现为意义不明的变异,或在乳腺癌风险相关性有疑问的基因中发现致病性变异。同时,谁来订购基因检测的人的角色也在发生变化,这将提高基因检测的可及性。这种基因检测的普及必须伴随着所有医疗保健提供者增加基因知识素养,并获得遗传专业人员的支持,以管理患者和高危家庭成员。

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