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Genetic influence of EGFR-PI3K-mTOR pathway and other loci in triple-negative breast cancer

Date

10 Oct 2016

Session

Poster display

Presenters

Carlos Cabrera

Citation

Annals of Oncology (2016) 27 (6): 15-42. 10.1093/annonc/mdw363

Authors

C. Cabrera1, M.J. Arranz2, M.L. Surralles Calnge3, A. Salas3, X. Tarroch3, L. Ibañez2, A. Garcia4, S. Gonzalez Jimenez1, M. Campayo1, L. Cirera1

Author affiliations

  • 1 Oncology And Hematology Department, Hospital Univeristari Mutua Terrassa, 08221 - Terrassa/ES
  • 2 Fundacio Docència I Recerca Mútua Terrassa, Hospital Univeristari Mutua Terrassa, 08221 - Terrassa/ES
  • 3 Pathology Department, Hospital Univeristari Mutua Terrassa, 08221 - Terrassa/ES
  • 4 Gynecology And Obstretics Department, Hospital Univeristari Mutua Terrassa, 08221 - Terrassa/ES
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Resources

Background

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.

Methods

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.

Results

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=

Conclusions

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

Funding

Hospital Universitari Mutua Terrassa

Disclosure

All authors have declared no conflicts of interest.

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