5% 至 10% 的乳腺癌病例与乳腺癌易感基因 (BCSG) 中的遗传性种系致病性或可能致病性变异 (GPV) 相关，这可能会改变局部和全身治疗建议。传统的基因检测标准遗漏了其中一部分病例。旨在评估新诊断乳腺癌的不同种族女性队列中 2 组 BCSG 中 GPV 的患病率和临床病理学关联。这项横断面研究于 2017 年在蒙特利尔的 3 家医院进行。 2019 年 9 月和 2022 年 4 月，为所有首次诊断出浸润性乳腺癌的女性提供了普遍的遗传咨询和检测。为女性提供了包含 BRCA1、BRCA2 和 PALB2 (B1B2P2) 的强制性主要面板以及包含 14 个额外 BCSG 的可选辅助面板。符合资格的参与者是年龄在 18 岁或以上、在转诊至研究前不超过 6 个月内被诊断为首次原发性浸润性乳腺癌的女性。数据分析时间为 2023 年 11 月至 2024 年 6 月。在 1017 名转诊患者中，805 名符合资格并提供遗传咨询和检测，这 805 名患者中有 729 名 (90.6%) 同意接受检测。乳腺癌诊断时的中位年龄为 53 岁（范围为 23-91 岁），其中 65.4% 为白人和欧洲血统。在 53 名患者 (7.3%) 中鉴定出 54 个 GPV，其中 39 名患者 (5.3%) 患有 B1B2P2，15 名患者 (2.1%) 患有 14 个二级组 BCSG 中的 6 个（ATM、BARD1、BRIP1、CHEK2、RAD51D 和STK11）。多变量分析显示，与 B1B2P2 阳性状态独立相关的临床因素包括诊断时年龄小于 40 岁（比值比 [OR]，6.83；95% CI，2.22-20.90）、三阴性乳腺癌（OR，3.19） ；95% CI，1.20-8.43）、高级别疾病（OR，1.68；95% CI，1.05-2.70）和卵巢癌家族史（OR，9.75；95% CI，2.65-35.85）。在 39 名 B1B2P2 阳性患者中，有 13 名 (33.3%) 适合接受聚（腺苷二磷酸核糖）聚合酶 (PARP) 抑制剂治疗。 在这项针对新诊断的浸润性乳腺癌女性的横断面通用基因检测研究中，GPV 的患病率为 7.3%，其中 5.3% 的患者 B1B2P2 检测呈阳性。在 B1B2P2 女性中，三分之一有资格接受 PARP 抑制剂治疗。

Between 5% and 10% of breast cancer cases are associated with an inherited germline pathogenic or likely pathogenic variant (GPV) in a breast cancer susceptibility gene (BCSG), which could alter local and systemic therapy recommendations. Traditional genetic testing criteria misses a proportion of these cases.To evaluate the prevalence and clinicopathological associations of GPVs in 2 groups of BCSGs among an ethnically diverse cohort of women with newly diagnosed breast cancer.This cross-sectional study, conducted at 3 Montreal hospitals between September 2019 and April 2022, offered universal genetic counseling and testing to all women with a first diagnosis of invasive breast cancer. Women were offered an obligatory primary panel of BRCA1, BRCA2, and PALB2 (B1B2P2) and an optional secondary panel of 14 additional BCSGs. Eligible participants were women 18 years of age or older who received a diagnosis of a first primary invasive breast cancer not more than 6 months before the time of referral to the study. Data were analyzed from November 2023 to June 2024.Of 1017 referred patients, 805 were eligible and offered genetic counseling and testing, and 729 of those 805 (90.6%) consented to be tested. The median age at breast cancer diagnosis was 53 years (range, 23-91 years), and 65.4% were White and of European ancestry. Fifty-four GPVs were identified in 53 patients (7.3%), including 39 patients (5.3%) with B1B2P2 and 15 patients (2.1%) with 6 of the 14 secondary panel BCSGs (ATM, BARD1, BRIP1, CHEK2, RAD51D, and STK11). On multivariable analysis, clinical factors independently associated with B1B2P2-positive status included being younger than 40 years of age at diagnosis (odds ratio [OR], 6.83; 95% CI, 2.22-20.90), triple-negative breast cancer (OR, 3.19; 95% CI, 1.20-8.43), high grade disease (OR, 1.68; 95% CI, 1.05-2.70), and family history of ovarian cancer (OR, 9.75; 95% CI, 2.65-35.85). Of 39 B1B2P2-positive patients, 13 (33.3%) were eligible for poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors.In this cross-sectional universal genetic testing study of women with newly diagnosed invasive breast cancer, the prevalence of GPVs was 7.3%, with 5.3% of patients testing positive for B1B2P2. Among B1B2P2-women women, one-third were eligible for PARP inhibitors.