背景：基因检测在指导筛查中起着重要作用，诊断,和精确治疗乳腺癌（BC）。然而,适当的基因检测标准仍然存在争议。本研究旨在通过分析大规模中国BC患者的种系突变谱和临床病理特征，促进制定合适的策略。
方法：对2014年9月至2022年3月在中山大学肿瘤防治中心（SYSUCC）接受基因检测的BC患者进行回顾性分析。在人群队列中应用并比较了不同的筛选标准。
结果：共纳入1035例BC患者，在235例患者中发现237例致病性或可能的致病性变异（P/LPV），包括203名患者中的41名（19.6%）只检测BRCA1/2基因，832人中有194人(23.3%)接受了21个基因小组测试。在235个P/LPV运营商中，222（94.5%）符合NCCN高风险标准，和13（5.5％）没有。在使用德赛的测试标准时，所有女性诊断为60岁的BC和老年患者的NCCN标准，234（99.6%）符合高风险标准，只有一个没有。21个基因小组测试确定了4.9％的非BRCAP/LPV和显着高比率的不确定显著性变异（VUS）（33.9％）。最常见的非BRCAP/LPV是PALB2（11，1.3％），TP53（10，1.2%），PTEN（3，0.4%），CHEK2（3，0.4%），ATM（3，0.4%），BARD1（3，0.4%），和RAD51C（2，0.2%）。与BRCA1/2P/LPV相比，非BRCAP/LPV显示NCCN标准列出的家族史的发生率显着低，第二原发癌,和不同的分子亚型。
结论：Desai的标准可能是更适合中国BC患者的基因检测策略。小组测试可以比单独的BRCA1/2测试识别更多的非BRCAP/LPV。与BRCA1/2P/LPV相比，非BRCAP/LPV表现出不同的癌症和分子亚型分布的个人和家族史。BC的最佳遗传检测策略仍需要进行更大的连续种群研究。
Genetic testing plays an important role in guiding screening, diagnosis, and precision treatment of breast cancer (BC). However, the appropriate genetic testing criteria remain controversial. The current study aims to facilitate the development of suitable strategies by analyzing the germline mutational profiles and clinicopathological features of large-scale Chinese BC patients.
BC patients who had undergone genetic testing at the Sun Yat-sen University Cancer Center (SYSUCC) from September 2014 to March 2022 were retrospectively reviewed. Different screening criteria were applied and compared in the population cohort.
A total of 1035 BC patients were enrolled, 237 pathogenic or likely pathogenic variants (P/LPV) were identified in 235 patients, including 41 out of 203 (19.6%) patients tested only for BRCA1/2 genes, and 194 out of 832 (23.3%) received 21 genes panel testing. Among the 235 P/LPV carriers, 222 (94.5%) met the NCCN high-risk criteria, and 13 (5.5%) did not. While using Desai\'s criteria of testing, all females diagnosed with BC by 60 years and NCCN criteria for older patients, 234 (99.6%) met the high-risk standard, and only one did not. The 21 genes panel testing identified 4.9% of non-BRCA P/LPVs and a significantly high rate of variants of uncertain significance (VUSs) (33.9%). The most common non-BRCA P/LPVs were PALB2 (11, 1.3%), TP53 (10, 1.2%), PTEN (3, 0.4%), CHEK2 (3, 0.4%), ATM (3, 0.4%), BARD1 (3, 0.4%), and RAD51C (2, 0.2%). Compared with BRCA1/2 P/LPVs, non-BRCA P/LPVs showed a significantly low incidence of NCCN criteria listed family history, second primary cancer, and different molecular subtypes.
Desai\'s criteria might be a more appropriate genetic testing strategy for Chinese BC patients. Panel testing could identify more non-BRCA P/LPVs than BRCA1/2 testing alone. Compared with BRCA1/2 P/LPVs, non-BRCA P/LPVs exhibited different personal and family histories of cancer and molecular subtype distributions. The optimal genetic testing strategy for BC still needs to be investigated with larger continuous population studies.
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