在家族乳腺癌（BC）的临床遗传检测中，基于人群遗传研究发现的低影响遗传变异通常不作为例行测量。我们研究了将已建立的多基因风险评分（Polygenic Risk Score，PRS）（BCAC 313, PRS313）融入瑞典家族性BC妇女的临床测序中的后果。我们开发了一个附加的测序板，用于在临床筛查遗传性BC基因的基础上捕获313个风险变异。通过比较PRS计算结果，纳入了来自87个家庭的无致病变异的索引患者和1000个人群对照。在包括详细家族病史、测序结果和肿瘤病理学信息的基础上，我们使用BOADICEA（乳腺和卵巢疾病发病率和携带者估计算法）V.6估算了不带和带有PRS313的对侧和终身风险。与人群对照相比，BC但在遗传性BC基因中没有致病变异的女性具有更高的PRS313（均值为0.78 SD，p < 3e-9）。如果在BC诊断前将PRS313纳入临床风险评估，将会改变24%-45%的女性的建议后续随访。我们的结果显示了将PRS313直接纳入家族性BC妇女的临床基因组调查中的潜在影响。 2023©作者或其雇主合法使用。CC BY-NC许可下允许再使用。由BMJ出版。

Low-impact genetic variants identified in population-based genetic studies are not routinely measured as part of clinical genetic testing in familial breast cancer (BC). We studied the consequences of integrating an established Polygenic Risk Score (PRS) (BCAC 313, PRS313) into clinical sequencing of women with familial BC in Sweden.We developed an add-on sequencing panel to capture 313 risk variants in addition to the clinical screening of hereditary BC genes. Index patients with no pathogenic variant from 87 families, and 1000 population controls, were included in comparative PRS calculations. Including detailed family history, sequencing results and tumour pathology information, we used BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) V.6 to estimate contralateral and lifetime risks without and with PRS313.Women with BC but no pathogenic variants in hereditary BC genes have a higher PRS313 compared with population controls (mean+0.78 SD, p<3e-9). Implementing PRS313 in the clinical risk estimation before their BC diagnosis would have changed the recommended follow-up in 24%-45% of women.Our results show the potential impact of incorporating PRS313 directly in the clinical genomic investigation of women with familial BC.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.