MAPK overexpression is associated with anthracycline resistance and increased risk for recurrence in patients with triple-negative breast cancer

Ann Oncol. 2008 Apr;19(4):669-74. doi: 10.1093/annonc/mdm522. Epub 2007 Nov 15.

Abstract

Background: Triple-negative breast cancer is estimated to account for 15%-20% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular factors in patients with triple-negative breast cancer.

Patients and methods: Tumor specimens from 109 patients with receptor-negative (estrogen receptor and progesterone receptor) breast cancer were analyzed for mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR) and phosphoinositol-3-kinase (PI3K) expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables, was investigated.

Results: Fifteen (13.8%), 38 (34.9%) and 33 patients (30.3%) had positive staining for EGFR, MAPK and PI3K, respectively. MAPK was associated with anthracycline resistance (P = 0.008) and lower MAPK score was significantly associated with shorter disease-free survival (P = 0.029). Survival following relapse was significantly worse for those with a higher MAPK score (P = 0.03).

Conclusion: MAPK is a significant prognostic and predictive factor in patients with triple-negative breast cancer. Furthermore, the level of staining among those with a positive MAPK expression may play a prognostic role at different stages of relapse. Further translational research is required to elucidate molecular mechanisms of tumor proliferation in this subset of patients.

MeSH terms

  • Adult
  • Aged
  • Anthracyclines / pharmacology*
  • Anthracyclines / therapeutic use
  • Antibiotics, Antineoplastic / pharmacology*
  • Antibiotics, Antineoplastic / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / enzymology*
  • Drug Resistance, Neoplasm*
  • ErbB Receptors / analysis
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Mitogen-Activated Protein Kinases / analysis*
  • Neoplasm Recurrence, Local / chemistry
  • Neoplasm Recurrence, Local / enzymology*
  • Odds Ratio
  • Phosphatidylinositol 3-Kinases / analysis
  • Prognosis
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Up-Regulation

Substances

  • Anthracyclines
  • Antibiotics, Antineoplastic
  • Biomarkers, Tumor
  • Phosphatidylinositol 3-Kinases
  • ErbB Receptors
  • Mitogen-Activated Protein Kinases