Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Division of Medical Genetics, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Cancer Rep (Hoboken). 2023 Jan;6(1):e1664. doi: 10.1002/cnr2.1664. Epub 2022 Jul 1.
Germline mutations in BRCA1/2 are the most common cause of hereditary breast and ovarian cancer (HBOC) syndrome. Few studies published during the past decade reported the prevalence of germline BRCA mutations in Asian patients with breast cancer. We aimed to assess the prevalence and characteristics of Thai patients with breast cancer with germline BRCA1/2 mutations.
We retrospectively reviewed all breast cancer patients who were tested for germline BRCA1/2 mutations during 2014-2018. BRCA mutations were detected using next-generation sequencing and confirmed using Sanger sequencing. We analyzed the characteristics of patients with or without BRCA mutations. Disease-free survival (DFS) and the associated factors were determined.
Among 67 patients, 12 (18%) were BRCA1/2 carriers (6 each), 4 (6%) harbored variants of uncertain significance, and 51 (76%) were non-carriers. We discovered two novel BRCA2 frameshift mutations (c.2380delA and c.8855dupT). Mean ages at breast cancer diagnosis of BRCA1, BRCA2, and non-carriers were 39.8, 46.2, and 42.0 years, respectively. The 12 tumors of BRCA carriers were mainly the luminal-B subtype. Two of these tumors were HER2-positive luminal-B, and the triple-negative subtype was not detected. After adjusting for stages and luminal subtypes, BRCA carriers experienced worse 3-year DFS than non-carriers (81.5% vs. 90.3%, HR 2.04 [0.64-6.49], p = .229). The stage at diagnosis was the sole factor significantly associated with 3-year DFS (100%, 84.8%, and 72.7%; stages I, II, and III, respectively).
Thai patients with breast cancer with BRCA1/2 mutations were mainly the luminal-B subtypes with worse prognosis than those without mutations.
BRCA1/2 种系突变是遗传性乳腺癌和卵巢癌（HBOC）综合征的最常见原因。过去十年发表的少数研究报告了亚洲乳腺癌患者种系 BRCA 突变的流行率。我们旨在评估泰国乳腺癌患者种系 BRCA1/2 突变的流行率和特征。
我们回顾性分析了 2014 年至 2018 年期间接受种系 BRCA1/2 突变检测的所有乳腺癌患者。使用下一代测序检测 BRCA 突变，并使用 Sanger 测序进行确认。我们分析了有或没有 BRCA 突变的患者的特征。确定无病生存（DFS）和相关因素。
在 67 名患者中，有 12 名（18%）是 BRCA1/2 携带者（各 6 名），4 名（6%）携带意义不明的变异，51 名（76%）是非携带者。我们发现了两种新的 BRCA2 移码突变（c.2380delA 和 c.8855dupT）。BRCA1、BRCA2 和非携带者的乳腺癌诊断平均年龄分别为 39.8、46.2 和 42.0 岁。12 名 BRCA 携带者的肿瘤主要为 luminal-B 亚型。其中 2 例肿瘤为 HER2 阳性 luminal-B，未检测到三阴性亚型。调整分期和 luminal 亚型后，BRCA 携带者的 3 年 DFS 较非携带者差（81.5% vs. 90.3%，HR 2.04 [0.64-6.49]，p=0.229）。诊断时的分期是与 3 年 DFS 显著相关的唯一因素（100%、84.8%和 72.7%；分别为 I 期、II 期和 III 期）。
泰国乳腺癌患者 BRCA1/2 突变主要为 luminal-B 亚型，预后较无突变者差。
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