Frequency of somatic and germline variants of predisposition genes in young Chinese women with breast cancer.

Purpose: Age stratification influences the clinicopathological features and survival outcomes of breast cancer. We aimed to understand the effect of age on gene variants in young Chinese women with breast cancer compared with those from The Cancer Genome Atlas (TCGA).

Methods: Enrolled patients ≤ 40 years old (N = 370) underwent germline or somatic genetic testing using a 32-gene hereditary cancer panel at Fujian Union Hospital. Significant alterations of germline and somatic genes were analyzed. The frequency of somatic variants was compared between enrolled patients and patients from TCGA who were divided into two groups (≤ 40 years and > 40 years).

Results: Among the enrolled patients (median age 36; range 25-40), 335 underwent germline genetic testing and 174 underwent simultaneous somatic genetic testing. We detected 44 germline pathogenic/likely pathogenic variants in 42 (12.5%) patients, where BRCA1/2 was the most common gene (29.8.5%). Family history of first-degree relatives was significantly associated with pathogenic variants (p < 0.001). Somatic Tier I/II mutation frequency was like that of patients ≤ 40 from TCGA (N = 97). More PIK3CA and TP53 mutations in luminal A and basal-like tumors, respectively, were detected in young patients than in patients > 40 from TCGA (N = 975). No significant differences were observed in other breast cancer subtypes.

Conclusion: These results provide a spectrum of genomic alterations in young Chinese women and highlight different frequencies of gene variants in young Asian patients versus Western patients with breast cancer. Further research should explore the biological mechanism to provide more treatment strategies for young Asian women.