Mutation study for high-risk breast and ovarian cancer (HBOC) has been extensively studied in patients of different ethnicities. Here we compared the germline mutation rate and mutation spectrum of patients (n= 4341) with benign breast diseases or breast cancers, with and without other risk factors. Three cohorts of Chinese patients were recruited. The first cohort, high-risk cohort (HR,n= 3935) included high-risk breast cancer patients fulfilling high-risk HBOC criteria and who are recruited at our genetics clinic. The second cohort, unselected cancer cohort (CC,n= 307) was from general recruitment of patients with breast cancer at breast surgery clinics. The third cohort, benign breast lesion cohort (NC,n= 99) comprised 99 patients with benign breast diseases such as fibroadenoma, fibroadenomatoid hyperplasia, and intraductal papilloma. Thirty HBOC related genes were sequenced on the above-mentioned patient cohorts. The germline mutation rates of HR, CC, and NC cohort were 11.9%, 6.5%, and 8.1%, respectively. In the CC cohort, 29.3% (90/307) of patients fulfilled the National Comprehensive Cancer Network (NCCN) high-risk genetic test criteria 2022 v.2. The mutation rate for this group of patients was 11.1%, similar to that of the HR cohort, while the mutation rate for those not fulfilling testing criteria was 4.6%, like that of the NC cohort. High penetrance genes (BRCA1/2,CDH1,PALB2,PTEN,andTP53) mutations were only found in the HR (10.6%) and CC (3.3%) cohorts but were not found in the NC cohort.ATM,BRIP1,RAD51C,andRAD51Dmutations were identified in all cohorts.RAD51CandRAD51Dmutations showed conflicting penetrance. An unexpectedly high mutation rate of total 2% was found in the NC cohort but it was only 0.3% and 0.5% in the HR cohort and CC cohort, respectively. Our results show a clinical need to enhance genetic testing of unselected breast cancer patients to identify the high-risk patients.
针对不同种族人群的高危乳腺癌和卵巢癌（HBOC）突变研究已得到广泛开展。本研究比较了伴有或不伴有其他风险因素的良性乳腺疾病或乳腺癌患者（n=4341）的胚系突变率及突变谱。研究共纳入三组中国患者队列：第一组为高危队列（HR，n=3935），包含符合高危HBOC标准且于我院遗传门诊招募的高危乳腺癌患者；第二组为非选择性癌症队列（CC，n=307），来源于乳腺外科门诊常规招募的乳腺癌患者；第三组为良性乳腺病变队列（NC，n=99），由99例患有纤维腺瘤、纤维腺瘤样增生及导管内乳头状瘤等良性乳腺疾病的患者组成。对上述患者队列进行了30个HBOC相关基因测序分析。HR、CC及NC队列的胚系突变率分别为11.9%、6.5%和8.1%。在CC队列中，29.3%（90/307）的患者符合美国国家综合癌症网络（NCCN）2022年第2版高危基因检测标准，该亚组患者的突变率为11.1%，与HR队列相近；而未达检测标准者的突变率为4.6%，与NC队列相似。高外显率基因（BRCA1/2、CDH1、PALB2、PTEN及TP53）突变仅见于HR（10.6%）和CC（3.3%）队列，NC队列中未检出。所有队列均发现ATM、BRIP1、RAD51C及RAD51D基因突变，其中RAD51C和RAD51D突变显示出不一致的外显率。值得注意的是，NC队列中总突变率意外高达2%，而HR与CC队列分别仅为0.3%和0.5%。本研究结果表明，有必要加强对非选择性乳腺癌患者的基因检测以识别高危人群。
肿瘤(癌症)患者之家