Background: Hereditary cancer predisposition syndromes are responsible for approximately 5–10% of all diagnosed cancer cases. In order to identify individuals at risk in a cost-efficient manner, family members of individuals carrying pathogenic alterations are tested only for the specific variant that was identified in their carrier relative. The purpose of this study was to investigate the clinical use and implementation of cascade family testing (CFT) in families of breast cancer patients with pathogenic/likely pathogenic variants (PVs/LPVs) in cancer-related predisposition genes. Methods: Germline sequencing was carried out with NGS technology using a 52-gene panel, and cascade testing was performed by Sanger sequencing or MLPA. Results: In a cohort of 1785 breast cancer patients (families), 20.3% were found to have PVs/LPVs. Specifically, 52.2%, 25.1%, and 22.7% of patients had positive findings in high-, intermediate-, and low-penetrance breast cancer susceptibility genes, respectively. Although CFT was recommended to all families, only 117 families (32.3%) agreed to proceed with genetic testing. Among the first-degree relatives who underwent CFT, 70.3% were female, and 108 of 121 (89.3%) were cancer free. Additionally, 42.7%, 36.7%, and 20.6% were offspring, siblings, and parents of the subject, respectively. Our data suggest that CFT was mostly undertaken (104/117, 88.8%) in families with positive findings in high-risk genes. Conclusions: Cascade family testing can be a powerful tool for primary cancer prevention by identifying at-risk family members. It is of utmost importance to implement genetic counseling approaches leading to increased awareness and communication of genetic testing results.
背景：遗传性癌症易感综合征约占所有确诊癌症病例的5-10%。为以经济高效的方式识别高危个体，仅对携带致病性变异的个体家属进行其患病亲属所携带特定变异的检测。本研究旨在探讨级联家族检测在携带癌症相关易感基因致病性/可能致病性变异的乳腺癌患者家庭中的临床应用与实施情况。方法：采用包含52个基因的二代测序技术进行胚系测序，并通过桑格测序或MLPA技术实施级联检测。结果：在1785例乳腺癌患者（家庭）队列中，20.3%检出致病性/可能致病性变异。具体而言，分别有52.2%、25.1%和22.7%的患者在高、中、低外显率乳腺癌易感基因中呈现阳性结果。尽管所有家庭均被建议进行级联家族检测，仅117个家庭（32.3%）同意接受基因检测。在接受检测的一级亲属中，70.3%为女性，121人中有108人（89.3%）未患癌症。其中42.7%、36.7%和20.6%分别为先证者的子女、兄弟姐妹及父母。数据显示级联家族检测主要在高风险基因阳性结果的家族中实施（104/117，88.8%）。结论：级联家族检测通过识别高危家庭成员，可成为癌症一级预防的有效工具。实施能提升基因检测结果认知度与沟通效率的遗传咨询策略至关重要。
肿瘤(癌症)患者之家