Breast cancer (BC) is the most frequent cancer in women. About 15% of all cases account for the most aggressive subtype: triple negative breast cancer (TNBC). TNBC biological heterogeneity has been explained in both gene expression profile studies and genome wide association studies (GWAS). Our study explores the role of single nucleotide polymorphisms (SNP) in TNBC. We hypothesized that new loci can confer risk and prognosis of TNBC, given its well-known tendency to genetic aberrations.
In this retrospective study, we genotyped a group of SNP in 111 paraffin-embedded tumor samples of patients diagnosed with TNBC (cases) and in 176 blood samples of healthy donors (controls). The SNP were selected from 5 genes (MAP3K1, PI3K, TERT, EGFR, and mTOR) known for their implication in TNBC and other types of cancer.
Univariate analysis with chi-square test comparing genotypic frequencies between cases and controls confirmed statistical significance in EGFR rs4947986 (p= 0.001) and TERT rs2736100 (p=
Our study found no prognostic significance of SNP for disease free survival (DFS) or overall survival (OS) in the multivariate analyses including TNM stage, axillary status, treatment (chemotherapy and/or radiotherapy) and age.
Our findings not only confirm the genetic influence of molecular pathways in EGFR, PI3K, mTOR and MAP3K1 but also reveal new loci for development of TNBC.
Having recognized new TERT and EGFR mutations in our cohort encourages us to keep unveiling plausible new pathways on carcinogenesis and treatment targets for TNBC. However, more translational studies are mandatory.
Clinical trial identification
Legal entity responsible for the study
Hospital Universitari Mutua Terrassa-Oncology and Hematology Department
Hospital Universitari Mutua Terrassa
All authors have declared no conflicts of interest.