Effect of tamoxifen on serum IL-18, vascular endothelial growth factor and nitric oxide activities in breast carcinoma patients

Clin Exp Immunol. 2004 Sep;137(3):546-51. doi: 10.1111/j.1365-2249.2004.02579.x.


Vascular endothelial growth factor (VEGF) is a multi-functional cytokine that has been suggested to be a major angiogenic factor in breast cancer. Nitric oxide (NO) is a potent biological molecule that participates in the multi-step process of carcinogenesis. Interleukin (IL)-18 has been shown to have potent anti-tumour effects. In this study, we investigated the effect of tamoxifen therapy on serum VEGF, NO and IL-18 activity in breast cancer patients. Serum levels of VEGF, nitrate + nitrite and IL-18 were measured in 34 postmenopausal breast cancer patients before and 3 months after the tamoxifen therapy. Both serum VEGF and IL-18 levels decreased after tamoxifen therapy (P = 0.051, P < 0.05, respectively). Serum VEGF levels increased in patients with endometrial thickness, while patients without endometrial thickness had a significant reduction in serum VEGF levels after therapy (P < 0.05). Serum nitrate + nitrite levels increased after the therapy, but this was not statistically significant (P > 0.05). A decrease in serum VEGF levels with tamoxifen therapy may be a reflection of reduced angiogenic activity in patients without endometrial thickness. The negative effect of tamoxifen therapy on IL-18, which is known to have a potent antitumour activity, may be related to the decreased tumour growth by induction of NO and reduction of VEGF activity as a feedback mechanism.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Endometrium / diagnostic imaging
  • Estrogen Receptor Modulators / therapeutic use*
  • Female
  • Humans
  • Interleukin-18 / blood*
  • Middle Aged
  • Neovascularization, Pathologic
  • Nitrates / blood
  • Nitric Oxide / metabolism*
  • Nitrites / blood
  • Tamoxifen / therapeutic use*
  • Ultrasonography
  • Vascular Endothelial Growth Factor A / blood*


  • Estrogen Receptor Modulators
  • Interleukin-18
  • Nitrates
  • Nitrites
  • Vascular Endothelial Growth Factor A
  • Tamoxifen
  • Nitric Oxide