Increased Identification of Candidates for High-Risk Breast Cancer Screening Through Expanded Genetic Testing
Increased Identification of Candidates for High-Risk Breast Cancer Screening Through Expanded Genetic Testing
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DOI：
10.1016/j.jacr.2016.10.003
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发表时间：
2017-04-01
影响因子：
4.5
通讯作者：
Manley, Susan
中科院分区：
文献类型：
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作者：
Rosenthal, Eric T.;Evans, Brent;Manley, Susan
目的：根据主要依赖于家族史的风险模型的估计，建议对乳腺癌终身风险>20%的女性进行乳腺MRI筛查。或者，通过BRCA 1和BRCA 2的基因检测，以及越来越多的与遗传性乳腺癌风险相关的其他基因的选择，可以确定>20%的终生风险。本研究的目的是量化BRCA 1/2以外的基因检测的影响，以及这些基因中的突变携带者在多大程度上被确定为仅基于家族史进行增强筛查的候选人。方法：女性接受了25个基因的遗传性癌症检测，包括BRCA 1/2和7个已知与>20%的癌症相关的基因。乳腺癌的终生风险（ATM、CHEK 2、PALB 2、TP 53、PTEN、CDH 1和STKI I）。对发现携带致病性变异（PV）的妇女进行Claus模型评估，根据家族史评估她们是否有>20%的终生风险。结果：在9,641名妇女中，共鉴定出9,751个PV。BRCA 1/2占肺静脉的59.1%，ATM、CHEK 2或PALB 2占38.8%。只有24.7%的所有妇女与PV发现在任何基因达到>20%的终身风险阈值使用克劳斯model.Conclusions：扩大基因检测超过BRCAI/2显着增加的妇女谁是乳腺MRI和其他风险降低措施的候选人，其中大多数人不会被确定通过家族史评估。
Purpose: Breast MRI screening is recommended for women with a >20% lifetime risk for breast cancer on the basis of estimates derived from risk models dependent largely on family history. Alternatively, a >20% lifetime risk can be established through genetic testing of BRCAI and BRCA2, as well as a growing selection of other genes associated with inherited breast cancer risk. The aim of this study was to quantify the impact of testing for genes other than BRCA 1/2 and the extent to which mutation carriers in these genes would have been identified as candidates for enhanced screening on the basis of family history alone.Methods: Women were tested with a 25-gene hereditary cancer panel including BRCA1/2 and 7 additional genes known to be associated with a >20% lifetime risk for breast cancer (ATM, CHEK2, PALB2, TP53, PTEN, CDH1, and STKI I). Women found to carry pathogenic variants (PVs) were evaluated with the Claus model to assess whether they would have been found to be at >20% lifetime risk on the basis of family history.Results: In total, 9,751 PVs in the selected breast cancer risk genes were identified in 9,641 women. BRCA1/2 accounted for 59.1% of the PVs, and 38.8% were in ATM, CHEK2, or PALB2. Only 24.7% of all women with PVs found in any gene reached the >20% lifetime risk threshold using the Claus model.Conclusions: Expanding genetic testing beyond BRCAI/2 significantly increases the number of women who are candidates for breast MRI and other risk reduction measures, most of whom would not have been identified through family history assessment.