State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
Cancer Med. 2023 Jun;12(12):13019-13030. doi: 10.1002/cam4.5976. Epub 2023 Apr 25.
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.
基因检测在指导乳腺癌（BC）的筛查、诊断和精准治疗方面发挥着重要作用。然而，合适的基因检测标准仍存在争议。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，为制定合适的策略提供帮助。
回顾性分析 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。在人群队列中应用了不同的筛查标准并进行了比较。
共纳入 1035 例 BC 患者，235 例患者中发现 237 个致病性或可能致病性变异（P/LPV），其中 41 例（19.6%）仅检测 BRCA1/2 基因，194 例（23.3%）接受 21 基因panel 检测。在 235 例 P/LPV 携带者中，222 例（94.5%）符合 NCCN 高危标准，13 例（5.5%）不符合。而使用 Desai 的检测标准时，所有 60 岁前诊断为 BC 的女性和 NCCN 标准用于老年患者，234 例（99.6%）符合高危标准，只有 1 例不符合。21 基因 panel 检测发现 4.9%的非 BRCA P/LPV 和显著高比例的意义不明变异（VUS）（33.9%）。最常见的非 BRCA P/LPV 是 PALB2（11 例，1.3%）、TP53（10 例，1.2%）、PTEN（3 例，0.4%）、CHEK2（3 例，0.4%）、ATM（3 例，0.4%）、BARD1（3 例，0.4%）和 RAD51C（2 例，0.2%）。与 BRCA1/2 P/LPV 相比，非 BRCA P/LPV 的 NCCN 标准列出的家族史、第二原发癌和不同分子亚型的发生率明显较低。
Desai 的标准可能是更适合中国 BC 患者的基因检测策略。与单独检测 BRCA1/2 相比，panel 检测可以识别更多的非 BRCA P/LPV。与 BRCA1/2 P/LPV 相比，非 BRCA P/LPV 表现出不同的个人和家族癌症史以及分子亚型分布。BC 的最佳基因检测策略仍需要通过更大规模的连续人群研究来探索。
