AimAlthough BRCA1/2 is most frequently associated with hereditary breast and ovarian cancer (HBOC), many other related genes have been implicated. Therefore, we investigated the prevalence of non‐BRCA1/2 genes associated with hereditary cancer predisposition in BRCA1/2‐negative patients from the Department of Genetic Medicine and Services with breast and ovarian cancer using a multi‐gene panel (MGP) analysis.MethodsWe conducted a retrospective MGP analysis (National Cancer Center Onco‐Panel for Familial Cancer; NOP_FC) in BRCA1/2‐negative patients with breast, ovarian, and overlapping breast/ovarian cancers who visited our genetic counseling between April 2004 and October 2022.ResultsNOP_FC was performed in 128 of the 390 BRCA test‐negative cases (117 breast cancer, 9 ovarian cancer, and 2 overlapping breast/ovarian cancer cases). Among the BRCA1/2‐negative patients, nine (7.7%) with breast cancer and one (11%) with ovarian cancer had pathogenic variants (PVs) in non‐BRCA1/2 genes associated with breast and ovarian cancers, respectively. Five patients had PVs in RAD51D, two in PALB2, one in BARD1, one in ATM, and one in RAD51C.ConclusionsAdditional MGP testing of germline genes associated with hereditary cancer predisposition syndrome in BRCA1/2‐negative breast and ovarian cancer patients revealed PVs in non‐BRCA1/2 breast cancer‐ and ovarian cancer‐related genes in 7.7% of breast cancer and 11% of ovarian cancer. Therefore, additional testing may provide useful information for subsequent risk‐reducing surgery and surveillance in BRCA1/2‐negative patients.

中文翻译：

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疑似遗传性乳腺癌和卵巢癌综合征的 BRCA1/2 阴性患者的多基因面板分析：来自单一机构的真实世界数据


目的尽管 BRCA1/2 最常与遗传性乳腺癌和卵巢癌 （HBOC） 相关，但许多其他相关基因也与此有关。因此，我们使用多基因面板 （MGP） 分析调查了遗传医学和服务部乳腺癌和卵巢癌 BRCA1/2 阴性患者中与遗传性癌症易感性相关的非 BRCA1/2 基因的患病率。方法我们进行了回顾性 MGP 分析（美国国家癌症中心 Onco-Panel for Familial Cancer;NOP_FC） 在 2004 年 4 月至 2022.ResultsNOP_FC 年 10 月期间访问我们的遗传咨询的 BRCA1/2 阴性乳腺癌、卵巢癌和重叠乳腺癌/卵巢癌患者中，在 390 例 BRCA 检测阴性病例中的 128 例（117 例乳腺癌、9 例卵巢癌和 2 例重叠乳腺癌/卵巢癌病例）进行了检查。在 BRCA1/2 阴性患者中，9 例 （7.7%） 乳腺癌患者和 1 例 （11%） 卵巢癌患者分别在与乳腺癌和卵巢癌相关的非 BRCA1/2 基因中存在致病性变异 （PV）。5 例患者 PVs 为 RAD51D，2 例为 PALB2,1 例为 BARD1,1 例为 ATM，1 例为 RAD51C。结论对 BRCA1/2 阴性乳腺癌和卵巢癌患者遗传性癌症易感综合征相关的种系基因进行额外的 MGP 检测，发现 7.7% 的乳腺癌和 11% 的卵巢癌患者在非 BRCA1/2 乳腺癌和卵巢癌相关基因中存在 PV。因此，额外的检测可能为 BRCA1/2 阴性患者的后续降低风险手术和监测提供有用的信息。