Activated PI3K/AKT and MAPK pathways are potential good prognostic markers in node-positive, triple-negative breast cancer

Ann Oncol. 2014 Oct;25(10):1973-1979. doi: 10.1093/annonc/mdu247. Epub 2014 Jul 9.

Abstract

Background: Triple-negative breast cancer (TNBC) patients are a poor prognostic subgroup, and currently, there is no biomarker for targeted therapy.

Patients and methods: Tissue samples were obtained from 75 TNBC patients with lymph-node metastases who had received adjuvant chemotherapy. We examined 11 biomarkers, including PIK3CA and AKT1mutation, with regard to event-free survival (EFS) and overall survival (OS) of patients.

Results: In the tumor tissues, phospho-AKT (pAKT) expression was significantly related to HER4 expression. Expression of each of these biomarkers was significantly related to longer EFS (P = 0.024 and 0.03, respectively). pERK expression was also a good prognostic factor regarding EFS and OS in TNBC (P = 0.002 and 0.006, respectively). We also identified a correlation between epidermal growth factor receptor positivity and insulin-like growth factor receptor type 1 positivity (P = 0.001). pERK and T-stage (1-3 versus >3) were independent good prognostic factors by multivariate analysis.

Conclusions: We determined that tumors expressing pAKT or pERK are a good prognostic subtype in node-positive TNBC. Different targeted therapies may be necessary for TNBC that involves activation of PI3K/AKT or MAPK pathways.

Keywords: HER4:PI3K; MAPK; biomarkers; prognosis; triple-negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Class I Phosphatidylinositol 3-Kinases
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Neoplasm Staging
  • Phosphatidylinositol 3-Kinases / biosynthesis*
  • Phosphatidylinositol 3-Kinases / genetics
  • Prognosis*
  • Proto-Oncogene Proteins c-akt / biosynthesis*
  • Proto-Oncogene Proteins c-akt / genetics
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-4 / biosynthesis
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology
  • Triple Negative Breast Neoplasms / therapy*

Substances

  • Biomarkers, Tumor
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ERBB4 protein, human
  • Receptor, ErbB-2
  • Receptor, ErbB-4
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase Kinases