与乳腺癌 (BC) 相关的高外显率基因（例如 BRCA1 和 BRCA2）致病性变异的管理已经很成熟。然而，中度外显率突变尚未得到充分研究。我们的目的是比较具有中等外显率 BC 相关基因突变且未事先进行 BC 诊断的患者的风险降低决策模式。 年龄≥ 18 岁且 BRCA1/2、高外显率或中外显率突变检测呈阳性的女性患者从单个学术中心的数据库中回顾性地确定了 1996 年至 2023 年间与 BC 相关且没有同时或先前诊断为 BC 的患者。按突变类型对组进行分层：BRCA1/2 突变（BRCA1、BRCA2）、高外显率突变（HPM；CDH1、PALB2、PTEN、STK11、TP53）或中等外显率突变（MPM；ATM、BARD1、CHEK2、NF1、RAD51C） ，RAD51D）。比较了人口统计学和临床​​结果。共有 528 名患者符合纳入标准，其中 66% (n = 350) 具有 BRCA1/2 突变，8% (n = 44) 具有 HPM，25% (n = 134)具有 MPM；中位随访时间为 56.0 个月。在我们的队列中，20.9% 的 BRCA 突变患者、9.1% 的 HPM 患者和 7.5% 的 MPM 患者选择接受降低风险的乳房切除术 (RRM)。在中等外显率队列中，选择接受 RRM 的患者在基因检测时年龄较小（39.4 岁 vs. 47.5 岁，p = 0.03），并且患有 BC 的家庭成员数量较多（2 vs. 1，p = 0.05） ）。我们的研究结果提供了对中度外显突变患者和寻求降低风险手术患者的人口特征和家族史的见解。© 2024。外科肿瘤学会。

Management of pathogenic variants in high penetrance genes related to breast cancer (BC), such as BRCA1 and BRCA2, are well established. However, moderate penetrance mutations are understudied. We aim to compare risk reduction decision-making patterns in patients with a moderate penetrance BC-related genetic mutations, without a prior BC diagnosis.Female patients aged ≥ 18 years who tested positive for a BRCA1/2, high penetrance, or moderate penetrance mutation related to BC between 1996 and 2023 without a concurrent or prior BC diagnosis were retrospectively identified from a single academic center's database. Groups were stratified by mutation type: BRCA1/2 mutations (BRCA1, BRCA2), high penetrance mutations (HPM; CDH1, PALB2, PTEN, STK11, TP53), or moderate penetrance mutations (MPM; ATM, BARD1, CHEK2, NF1, RAD51C, RAD51D). Demographics and clinical outcomes were compared.A total of 528 patients met the inclusion criteria, with 66% (n = 350) having a BRCA1/2 mutation, 8% (n = 44) having HPM, and 25% (n = 134) having MPM; the median follow-up was 56.0 months. In our cohort, 20.9% of patients with BRCA mutations, 9.1% with HPM, and 7.5% with MPM chose to undergo risk-reducing mastectomies (RRM). Within the moderate penetrance cohort, patients who chose to undergo RRM were younger at the time of genetic testing (39.4 vs. 47.5 years, p = 0.03) and had a higher number of family members with BC (2 vs. 1, p = 0.05).Our findings provide insights into the demographic characteristics and family history of patients with moderate penetrance mutations and those who pursue risk-reducing surgery.© 2024. Society of Surgical Oncology.