Characterization of Frequently Mutated Cancer Genes and Tumor Mutation Burden in Chinese Breast Cancer

OBJECTIVES: Various genomic alterations and genomic signatures, including ERBB2 amplification, mutations in PIK3CA, AKT1, and ESR1, and tumor mutational burden (TMB), have become important biomarkers for treatment selection in breast cancer (BC). This study aimed to investigate the mutational features of Chinese early-stage BC patients. METHODS: Tumors and matched blood samples collected from 589 Chinese patients with early-stage BC were sequenced using a commercial gene panel consisting of 520 cancer-related genes to analyze all types of genomic alterations and estimate the TMB status. RESULTS: A total of 18 genes were found to be more frequently mutated (P<0.05) or amplified (P<0.05) in stage T3–4 tumors as compared with T1–2 tumors. A total of 18 genes were found to be differentially mutated (P<0.05) or amplified (P<0.05) in patients with lymph node metastasis than those without lymph node metastasis. Younger patients (≤35 years) were more frequently identified with mutations or gene amplifications in eleven genes (P<0.05). TMB >10mutations/Mb were found in 5.7% of our cohort. Although the TMB was similar for various molecular subtypes between our cohort and the BC cohort of The Cancer Genome Atlas (TCGA) study, the TMB were statistically different for HR+/HER-, HR+/HER2+, and triple-negative subtypes between our cohort and African Americans in the TCGA study. As compared to the TCGA BC cohort, our cohort had a much earlier median age of diagnosis (48 vs. 58 years, P<0.001), and had significantly lower frequency of triple-negative subtype (11.5% vs. 18.4%, P<0.001) and invasive lobular BC (2.4% vs. 19.0%, P<0.001). Further subgroup analyses revealed that mutation rates in various genes including TP53, ERBB2, and PIK3CA were distinct for patients who were younger (≤35 years), had triple-negative or invasive lobular BC in our cohort than in the TCGA cohort. CONCLUSIONS: This study revealed distinct mutational features of various molecular subtypes of early-stage BC among Chinese patients. Moreover, we provide new insights into the differences in early-stage BC between the East and West.