The transcription factor CBFB mutations indicate an improved survival in HR+/HER2- breast cancer

Background: As a critical transcription factor, CBFB (core binding factor subunit β) is frequently mutated in breast cancer and considered to be of significance in the pathogenesis of cancer. The objective of this study was to investigate CBFB mutation profiles and the relationship between CBFB mutations and clinicopathologic characteristics in breast cancer.

Methods: A total of 671 treatment-naive Chinese patients with invasive breast cancer at Guangdong Provincial People's Hospital (GDPH) were recruited in this study. CBFB mutation status were detected using the method of capture-based targeted sequencing. Correlation between CBFB mutations and clinicopathologic features were analyzed. Then, we compared the results between Chinese and western population by using Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort (n = 1979) and The Cancer Genome Atlas (TCGA) cohort (n = 925).

Results: The prevalence of CBFB mutation in GDPH cohort, METABRIC cohort, and TCGA cohort was 4.6% (31/671), 4.6% (92/1979), 2.5% (23/925), respectively. A hotspot mutation due to nucleotide thymine duplication or deletion occurring at the exon2/3 junction was detected in the GDPH and METABRIC cohorts. CBFB mutations were found to be significantly associated with the subtype of HR+/HER2- breast cancer (P = 0.008 in GDPH cohort and P＜0.001 in METABRIC cohort), lower tumor grade (P = 0.004 in GDPH cohort and P＜0.001 in METABRIC cohort), lower expression of Ki-67 protein (P＜0.001 in GDPH cohort), but we didn't find similar results in TCGA cohort. In addition, CBFB in GDPH cohort was observed at a rather high mutation rate in invasive lobular carcinomas (4/18, 22.2%). Further, cox multivariate analysis demonstrated that CBFB was of independent prognosis significance in HR+/HER2- subgroup in METABRIC cohort (HR, 0.562; 95% CI, 0.399-0.790; P = 0.001).

Conclusion: This study reveals race diversity of CBFB mutation spectrum in breast cancers. CBFB mutations mainly occur in HR+/HER2- breast cancer, and it may be a promising prognostic biomarker in HR+/HER2- subgroup.