Open AccessGermline mutation in DNA ‐repair genes is associated with poor survival in BRCA 1/2‐ negative breast cancer patients
Author(s) -
Fan Zhenhua,
Hu Li,
Ouyang Tao,
Li Jinfeng,
Wang Tianfeng,
Fan Zhaoqing,
Fan Tie,
Lin Benyao,
Xu Ye,
Xie Yuntao
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14175
Subject(s) - breast cancer , germline mutation , dna repair , medicine , germline , cancer , oncology , cancer research , hazard ratio , brca mutation , mutation , biology , gene , genetics , confidence interval
BRCA 1/2 genes are the most frequently germline mutated DNA ‐repair genes, and the survival of BRCA 1/2 carriers has been extensively explored in breast cancer. However, the prevalence of germline mutations in non‐ BRCA 1/2 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 BRCA 1/2 ‐negative breast cancer patients who were unselected for family history of cancer or age at diagnosis. Among the 7657 BRCA 1/2 ‐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 BRCA 1/2 ‐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.