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中国乳腺癌患者错配修复基因致病性种系变异的临床相关性

Clinical relevance of pathogenic germline variants in mismatch repair genes in Chinese breast cancer patients.

作者信息

Hu Li, Sun Jie, Li Zhongwu, Qu Ziwei, Liu Yan, Wan Qiting, Liu Jiaming, Ding Xinyun, Zang Fan, Zhang Juan, Yao Lu, Xu Ye, Wang Yin, Xie Yuntao

机构信息

Familial & Hereditary Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, 100142, Beijing, P. R. China.

Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, 100142, Beijing, P. R. China.

出版信息

NPJ Breast Cancer. 2022 Apr 21;8(1):52. doi: 10.1038/s41523-022-00417-x.

DOI:10.1038/s41523-022-00417-x
PMID:35449176
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9023502/
Abstract

The prevalence and clinical relevance of pathogenic germline variants in MMR genes have not been investigated in large series of breast cancers. In this study, we screened the germline variants in MMR genes in 8085 consecutive Chinese breast cancer patients, and investigated the MMR/PD-L1 protein expression and tumor mutation burden (TMB) of breast tumors from MMR variant carriers. We found that 15 of 8085 patients (0.19%) carried a pathogenic germline variant in MMR genes. Compared with non-carriers, MMR variant carriers might have worse recurrence-free survival (unadjusted hazard ratios [HR] = 2.70, 95% CI: 1.12-6.49, P = 0.027) and distant recurrence-free survival (unadjusted HR = 3.24, 95% CI: 1.45-7.22, P = 0.004). More importantly, some of the breast cancers from MMR carriers displayed MMR protein loss (5/13), TMB-high (2/10), and PD-L1 positive expression (9/13). This study showed that MMR variant carriers were rare in breast cancer. They might have worse survival and part of them might benefit from immunotherapy.

摘要

错配修复（MMR）基因中致病种系变异的患病率及其临床相关性尚未在大量乳腺癌病例中进行研究。在本研究中，我们筛查了8085例连续的中国乳腺癌患者MMR基因中的种系变异，并研究了MMR变异携带者的乳腺肿瘤中MMR/程序性死亡受体配体1（PD-L1）蛋白表达及肿瘤突变负荷（TMB）。我们发现，8085例患者中有15例（0.19%）携带MMR基因的致病种系变异。与非携带者相比，MMR变异携带者的无复发生存期可能更差（未调整风险比[HR]=2.70，95%置信区间：1.12-6.49，P=0.027），远处无复发生存期也更差（未调整HR=3.24，95%置信区间：1.45-7.22，P=0.004）。更重要的是，MMR携带者的一些乳腺癌表现出MMR蛋白缺失（5/13）、TMB高（2/10）和PD-L1阳性表达（9/13）。本研究表明，MMR变异携带者在乳腺癌中很罕见。他们的生存可能更差，其中一部分人可能从免疫治疗中获益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69e2/9023502/71d568b3fe5a/41523_2022_417_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69e2/9023502/0f9dc24dd3d1/41523_2022_417_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69e2/9023502/449efb431793/41523_2022_417_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69e2/9023502/71d568b3fe5a/41523_2022_417_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69e2/9023502/0f9dc24dd3d1/41523_2022_417_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69e2/9023502/449efb431793/41523_2022_417_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69e2/9023502/71d568b3fe5a/41523_2022_417_Fig3_HTML.jpg

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