Background CHEK2 has been recognized as a breast cancer risk gene with moderate effect. Women who have previously tested negative for a BRCA1/2 gene germline pathogenic variant may benefit from additional genetic testing for the CHEK2 c.1100del pathogenic variant. The aims of this study were: 1) to assess the uptake of an active approach by recontacting BRCA1/2 -negative women for additional CHEK2 c.1100del testing on stored DNA-samples and 2) to explore patients’ experiences with this approach. Methods Between 2015 and 2017, women who had been tested earlier negative for BRCA1/2 germline pathogenic variants, were recontacted for additional CHEK2 c.1100del testing on stored DNA-samples, free-of-charge. They received an information letter about the CHEK2 pathogenic variant and could return an informed consent form when they opted for additional genetic testing. Those in whom the CHEK2 pathogenic variant was absent, received a letter describing this result. Those who tested positive, were invited for a personal counseling at the department of genetics. On average 21 months (range 4–27) after the genetic test result, a questionnaire was sent to all identified carriers and a control group of women who tested negative for the pathogenic variant to explore patients’ experiences with our approach. Results In total, 70% ( N = 1666) of the N = 2377 women contacted opted for additional testing, and 66 (4%) of them proved to be carriers of the CHEK2 c.1100del pathogenic variant. Regardless of the outcome of the genetic test, women were generally satisfied with our approach and reported that the written information was sufficient to make an informed decision about the additional CHEK2 testing. Conclusions The uptake (70%) of our approach was considered satisfactory. Patients considered the benefits more important than the psychosocial burden. Given the rapid developments in DNA-diagnostics, our findings may support future initiatives to recontact patients about additional genetic testing when they previously tested negative for a pathogenic variant in a breast cancer gene.

中文翻译：

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重新联系非 BRCA1/2 乳腺癌患者进行生殖系 CHEK2 c.1100del 致病性变异检测：摄取和患者体验

背景CHEK2已被公认为具有中等作用的乳腺癌风险基因。先前对 BRCA1/2 基因种系致病性变异检测为阴性的女性可能会受益于额外的 CHEK2 c.1100del 致病性变异基因检测。本研究的目的是：1) 通过重新联系 BRCA1/2 阴性女性对储存的 DNA 样本进行额外的 CHEK2 c.1100del 测试来评估积极方法的采用情况，以及 2) 探索患者对这种方法的体验。方法 在 2015 年至 2017 年期间，之前被检测为 BRCA1/2 种系致病性变异阴性的女性被重新联系，对储存的 DNA 样本进行额外的 CHEK2 c.1100del 检测，免费。他们收到了一封关于 CHEK2 致病性变异的信息信，并且在他们选择进行额外的基因检测时可以返回一份知情同意书。那些不存在 CHEK2 致病性变异的人收到了一封描述这一结果的信。那些检测呈阳性的人被邀请到遗传学部门进行个人咨询。在基因检测结果出炉后平均 21 个月（4-27 个月），我们会向所有鉴定出的携带者和一组对致病性变异检测呈阴性的女性发送问卷，以探索患者对我们方法的体验。结果 总共有 70% (N = 1666) 的 N = 2377 名女性选择了额外的检测，其中 66 (4%) 名被证明是 CHEK2 c.1100del 致病性变异的携带者。无论基因检测结果如何，女性普遍对我们的方法感到满意，并报告说书面信息足以就额外的 CHEK2 检测做出明智的决定。结论 我们的方法的采用率 (70%) 被认为是令人满意的。患者认为好处比社会心理负担更重要。鉴于 DNA 诊断学的快速发展，我们的研究结果可能支持未来的举措，当他们之前对乳腺癌基因的致病性变异检测为阴性时，重新联系患者进行额外的基因检测。