Overexpression of c-erbB-2 is related to a higher expression of vascular endothelial growth factor (VEGF) and constitutes an independent prognostic factor in primary node-positive breast cancer after adjuvant systemic treatment

Eur J Cancer. 2004 Jan;40(1):33-42. doi: 10.1016/s0959-8049(03)00673-7.


The aim of this study was to investigate possible associations between the expression of c-erbB-2 and the angiogenic factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), p53 status, routine breast cancer prognostic factors and survival. Expression of c-erbB-2, VEGF, bFGF, and p53 protein was determined with an enzyme-linked immunosorbent assay (ELISA) in 656 patients with primary breast cancer (median follow-up time of 83 months). In 60 cases, we also used immunohistochemistry (IHC) for c-erbB-2 evaluation, to be used as a reference for the ELISA. Overexpression of c-erbB-2 was significantly related to a higher expression of VEGF, lower bFGF content, negative steroid receptor status, and a high S-phase fraction. In multivariate analysis, c-erbB-2 was an independent prognostic factor for relapse-free survival (RFS) and overall survival (OS) in all patients, and in node-positive patients, irrespective of the adjuvant systemic therapy. Combined survival analyses regarding c-erbB-2 and VEGF yielded additional prognostic information.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / therapy
  • Carcinoma, Lobular / metabolism*
  • Carcinoma, Lobular / mortality
  • Carcinoma, Lobular / therapy
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Fibroblast Growth Factor 2 / metabolism
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis
  • Neoplasm Recurrence, Local
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Regression Analysis
  • Sweden / epidemiology
  • Tumor Suppressor Protein p53 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism*


  • Tumor Suppressor Protein p53
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Receptor, ErbB-2