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 2769 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 2769 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 non‐carriers (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 non‐carriers. 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 with non‐carriers.

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