Tumor-specific VEGF-A and VEGFR2 in postmenopausal breast cancer patients with long-term follow-up. Implication of a link between VEGF pathway and tamoxifen response

Breast Cancer Res Treat. 2005 Jan;89(2):135-43. doi: 10.1007/s10549-004-1655-7.

Abstract

Vascular endothelial growth factor (VEGF-A) is considered a prognostic indicator for clinical outcome in breast cancer. Conflicting results nevertheless exist and there is a need for larger studies including untreated patients in order to clarify the importance of tumor-specific VEGF-A regarding prognosis as well as potential links to predictive treatment information. VEGF-A and its receptor, vascular endothelial growth receptor 2 (VEGFR2), were therefore analyzed by immunohistochemistry in postmenopausal breast cancers enrolled in a clinical trial where patients were randomized to adjuvant tamoxifen treatment (n = 124) for 2 years or no treatment (n = 127) with a median follow-up of 18 years. The tumors were arranged in a tumor tissue microarray system enabling parallel analysis of the angiogenic factors and hormone receptor status. Tumor-specific expression of VEGFR2 correlated strongly with expression of VEGF-A and progesterone receptor (PR) negativity, whereas VEGF-A was not associated with hormone receptor status. Among patients with estrogen receptor (ER) positive (fraction > 10%) tumors, there was a statistically significant tamoxifen response in VEGF-A negative tumors at both 10-year and 18-year disease-free survival (DFS), contrasting to VEGF-A positive tumors who had no beneficial effect of tamoxifen. A treatment-interaction variable indicated a marked difference in tamoxifen response depending on VEGFA-status in terms of DFS at 10 and 18 years of follow-up, p = 0.046 and p = 0.039, respectively. VEGFR2 status did not yield significant predicitve information for tamoxifen response in patients with ER fraction > 10%, whereas in patients with ER fraction > 90% both VEGF-A and VEGFR2 status were associated with tamoxifen treatment effect.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology*
  • Chemotherapy, Adjuvant
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Postmenopause
  • Prognosis
  • Tamoxifen / pharmacology*
  • Tamoxifen / therapeutic use*
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / blood*
  • Vascular Endothelial Growth Factor Receptor-2 / blood*

Substances

  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Vascular Endothelial Growth Factor A
  • Tamoxifen
  • Vascular Endothelial Growth Factor Receptor-2