Prevalence of BRCA1 and BRCA2 pathogenic variants in 8627 unselected patients with breast cancer: stratification of age at diagnosis, family history and molecular subtype

• Published in: Breast cancer research and treatment Vol. 195; no. 3; pp. 431 - 439
• Main Authors: Zang, Fan, Ding, Xinyun, Chen, Jiuan, Hu, Li, Sun, Jie, Zhang, Juan, Xu, Ye, Yao, Lu, Xie, Yuntao
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2022; Springer; Springer Nature B.V
• Subjects: Age; BRCA1 protein; BRCA2 protein; Breast cancer; Cancer; Cancer patients; Cancer research; Care and treatment; Diagnosis; DNA sequencing; Epidemiology; ErbB-2 protein; Family medical history; Genetic aspects; Medicine; Medicine & Public Health; Next-generation sequencing; Nucleotide sequencing; Oncology; Ovarian cancer; Pancreatic cancer; Patients; Phenotypes; Prostate cancer; Chinese population; BRCA1/2 mutation; Breast cancer
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-022-06702-4

Purpose Comprehensively analyzing the prevalence of BRCA1/2 germline pathogenic variants (PVs) in a large cohort of unselected Chinese patients with breast cancer has great clinical importance. Methods Germline pathogenic variants in full-length BRCA1/2 genes were determined through next-generation sequencing and/or Sanger sequencing assays in 8627 unselected Chinese patients with breast cancer who were treated at the Breast Center of Peking University Cancer Hospital. The prevalence of BRCA1/2 PVs was further stratified by age at diagnosis, family history of cancer and molecular subtype. Results We found that the overall prevalence of BRCA1/2 PVs was 6.0% in the entire cohort, 2.4% in BRCA1 and 3.7% in BRCA2 . The prevalence of BRCA1/2 PVs in patients with early-onset breast cancer (age at diagnosis ≤ 40 years) was significantly higher than that in patients over the age of 40 (9.7% vs. 5.1%). The prevalence rates of BRCA1/2 PVs in patients with a family history of breast, ovarian, pancreatic, and prostate cancer were 19.5%, 39.0%, 11.1%, and 12.8%, respectively. Moreover, the number of relatives affected by breast cancer was associated with a higher prevalence of BRCA1/2 PVs. Molecular subtypes were associated with the prevalence of BRCA1/2 PVs. Patients with the triple-negative phenotype had the highest prevalence of BRCA1/2 PVs (13.3%) among the three molecular groups, followed by the HR + and HER2- group (5.9%), and the lowest was in the HER2 + group (2.5%). Conclusion Our study provides the most comprehensive information to date on the prevalence of BRCA1/2 PVs in unselected Chinese patients with breast cancer.