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. 2019 Oct;110(10):3368-3374.
doi: 10.1111/cas.14175. Epub 2019 Sep 19.

Germline mutation in DNA-repair genes is associated with poor survival in BRCA1/2-negative breast cancer patients

Zhenhua Fan  1 , Li Hu  1 , Tao Ouyang  1 , Jinfeng Li  1 , Tianfeng Wang  1 , Zhaoqing Fan  1 , Tie Fan  1 , Benyao Lin  1 , Ye Xu  1 , Yuntao Xie  1
Affiliations

Germline mutation in DNA-repair genes is associated with poor survival in BRCA1/2-negative breast cancer patients

Zhenhua Fan et al. Cancer Sci. 2019 Oct.

Abstract

BRCA1/2 genes are the most frequently germline mutated DNA-repair genes, and the survival of BRCA1/2 carriers has been extensively explored in breast cancer. However, the prevalence of germline mutations in non-BRCA1/2 DNA-repair genes and the survival of carriers are largely unknown in a large cohort of unselected breast cancer patients. Germline mutations in 16 DNA-repair genes were determined using a multigene panel in 7657 BRCA1/2-negative breast cancer patients who were unselected for family history of cancer or age at diagnosis. Among the 7657 BRCA1/2-negative breast cancer patients, 257 (3.4%) carried at least 1 pathogenic germline mutation in the 16 DNA-repair genes. The prevalence of DNA-repair gene mutations was significantly higher in familial breast cancers (5.2%, P = 0.002) and early-onset breast cancers (diagnosed at and before the age of 40) (4.5%, P = 0.003) than that of sporadic breast cancers (2.9%) (diagnosed above age of 40), respectively. The DNA-repair gene mutation carriers were significantly more likely to have a larger tumor (P = 0.04) and axillary lymph node metastasis (P = 0.03). Moreover, DNA-repair gene mutation was an independent unfavorable factor for recurrence-free survival (adjusted hazard ratio [HR] = 1.38, 95% CI: 1.00-1.91, P = 0.05) and disease-specific survival (adjusted HR=1.63, 95% CI: 1.04-2.57, P = 0.03) in this cohort. Overall, 3.4% of BRCA1/2-negative breast cancer patients carried germline mutations in the 16 DNA-repair genes, and the DNA-repair gene mutation carriers exhibited an aggressive phenotype and had poor survival compared with noncarriers.

Keywords: DNA-repair genes; breast cancer; cancer susceptibility genes; germline mutations; survival.

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Figures

Figure 1
Figure 1
Survival analyses by Kaplan‐Meier according to germline mutation status in 16 DNA‐repair genes. Panel A and B show recurrence‐free survival and disease‐specific survival, respectively
See this image and copyright information in PMC

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