不确定意义变体(VUS)的不当医疗使用仍然是遗传性癌症基因检测中的一个问题。这项研究的目的是评估致病性和可能致病性(P/LP)之间的关联。VUS,良性和可能良性(B/LB)基因检测结果以及癌症相关的手术和筛查管理。Medline的系统搜索,Embase,EBSCOCINAHLPlus,和PsycINFO于1946年至2020年8月26日进行。符合条件的研究包括具有癌症基因检测结果和手术或筛查管理结果的个体。我们回顾了885篇摘要和22项报告相关手术和筛查结果的研究。Meta分析显示,对于治疗性乳房切除术和对侧预防性乳房切除术,P/LP患者的手术率明显高于VUS患者(OR=7.35,95%CI,4.14-13.64)。预防性乳房切除术(OR=3.05,95%CI,1.5-6.19),卵巢切除术(OR=6.46,95%CI,3.64-11.44)。治疗性乳房切除术没有显着差异,或患有P/LP和VUS的个体之间的乳房保护或乳房切除术率,或VUS和B/LB患者之间的任何结果。评估筛查结果的研究有限,结果相互矛盾。综合分析并不表明大量有VUS结果的个体经历了不适当的临床管理。
Improper medical use of variant of uncertain significance (VUS) remains a concern in hereditary cancer genetic testing. The goal of this study was to assess the association between pathogenic and likely pathogenic (P/LP), VUS, and benign and likely benign (B/LB) genetic test results and cancer-related surgical and screening management. Systematic searches of Medline, Embase, EBSCO CINAHL Plus, and PsycINFO were conducted from 1946 to August 26, 2020. Eligible studies included individuals with cancer genetic test result and surgical or screening management outcomes. We reviewed 885 abstracts and 22 studies that reported relevant surgical and screening outcomes were included. Meta-analysis revealed significantly higher surgical rates among individuals with P/LP than among those with VUS for therapeutic mastectomy with contralateral prophylactic mastectomy (OR = 7.35, 95% CI, 4.14-13.64), prophylactic mastectomy (OR = 3.05, 95% CI, 1.5-6.19), and oophorectomy (OR = 6.46, 95% CI, 3.64-11.44). There were no significant differences in therapeutic mastectomy, or breast conservation or lumpectomy rates between individuals with P/LP and VUS, or in any outcomes between patients with VUS and B/LB. Studies evaluating screening outcomes were limited, and results were conflicting. Comprehensive analysis do not indicate that a significant number of individuals with VUS results undergo inappropriate clinical management.