Significantly higher levels of vascular endothelial growth factor (VEGF) and shorter survival times for patients with primary operable triple-negative breast cancer

Ann Oncol. 2009 Oct;20(10):1639-46. doi: 10.1093/annonc/mdp062. Epub 2009 Jun 23.

Abstract

Background: Triple-negative breast cancer (TNBC) lacking expression of steroid receptors and human epidermal growth factor receptor 2, having chemotherapy as the only therapeutic option, is characterised by early relapses and poor outcome. We investigated intratumoural (i.t.) levels of the pro-angiogenic cytokine vascular endothelial growth factor (VEGF) and survival in patients with TNBC compared with non-TNBC.

Patients and methods: VEGF levels were determined by an enzyme immunosorbent assay in a retrospective series consisting of 679 consecutive primary breast cancer patients.

Results: Eighty-seven patients (13%) were classified as TNBC and had significantly higher VEGF levels; median value in TNBC was 8.2 pg/microg DNA compared with 2.7 pg/microg DNA in non-TNBC (P < 0.001). Patients with TNBC had statistically significant shorter recurrence-free survival [hazard ratio (HR) = 1.8; P = 0.0023], breast cancer-corrected survival (HR = 2.2; P = 0.004) and overall survival (HR = 1.8; P = 0.005) compared with non-TNBC. Patients with TNBC relapsed earlier than non-TNBC; mean time from diagnosis to first relapse was 18.8 and 30.7 months, respectively. The time between first relapse and death was also shorter in TNBC: 7.5 months versus 17.5 months in non-TNBC (P = 0.087).

Conclusions: Our results show that TNBC have higher i.t. VEGF levels compared with non-TNBC. Ongoing clinical trials will answer if therapy directed towards angiogenesis may be an alternative way to improve outcome in this poor prognosis group.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neovascularization, Pathologic / genetics
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / analysis
  • Receptors, Estrogen / genetics
  • Receptors, Progesterone / analysis
  • Receptors, Progesterone / genetics
  • Survival Analysis
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / analysis
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Receptors, Estrogen
  • Receptors, Progesterone
  • Vascular Endothelial Growth Factor A
  • Receptor, ErbB-2