Prevalence and clinical outcomes of germline mutations in BRCA1/2 and PALB2 genes in 2769 unselected breast cancer patients in China

To gain more information on the prevalence of germline mutations in BRCA1/2 and PALB2 genes in the Chinese population, and to explore the effects of the mutation status of these genes on clinical outcomes in patients with breast cancer, we performed a screening for BRCA1/2 and PALB2 mutations in a consecutive series of unselected breast cancer patients in the Chinese population. A total of 2,769 cases were enrolled between June 1993 and September 2017. All of the exons and exon-intron boundaries of the BRCA1/2 and PALB2 genes were screened with next-generation sequencing. Of the 2,769 breast cancer patients, BRCA1, BRCA2 and PALB2 mutations accounted for 2.7% (n = 74), 2.7% (n = 76), and 0.9% (n = 24), respectively. The BRCA1 gene had the highest mutation frequency in patients with triple-negative breast cancer (TNBC), which was 9.6% (n = 42), while the BRCA2 gene had the highest mutation frequency in patients with Luminal, which was 3.2% (n = 58). The disease-free survival (DFS) of BRCA1 mutation carriers was significantly lower than that of noncarriers (adjusted HR = 2.20, 95% CI = 1.15-4.18, p = 0.017). The mutation status of the PALB2 gene was significantly associated with the decline in overall survival (OS) (adjusted HR = 8.38, 95% CI = 2.19-32.11, p = 0.002). No significant difference was found between BRCA2 pathogenic mutation carriers and noncarriers. These results demonstrate that BRCA1 mutation status may be associated with a worse disease progression in patients with breast cancer, and women who harbored a PALB2 mutation might be at a higher risk of death due to breast cancer compared to noncarriers.