The effects of standard anthracycline-based chemotherapy on soluble ICAM-1 and vascular endothelial growth factor levels in breast cancer

Clin Cancer Res. 2004 Aug 1;10(15):4998-5003. doi: 10.1158/1078-0432.CCR-0734-04.

Abstract

Purpose: The circulating soluble form of intercellular adhesion molecule-1 (sICAM-1) and vascular endothelial growth factor (VEGF) are elevated in women with breast cancer and associated with tumor progression and poor prognosis. This study examined the effects of anthracycline-based chemotherapy on plasma sICAM-1 and VEGF, as well as soluble P-selectin, von Willebrand factor, and interleukin-6 levels.

Experimental design: Twenty-six women diagnosed with stage I-IIIA breast cancer (mean age, 48.4 +/- 10.4 years; range, 34-79 years) were studied before (week 1) and at weeks 2 and 3 of cycles 1 and 4 of chemotherapy.

Results: The initial effect of chemotherapy was to reduce sICAM-1 levels; compared with pretreatment, sICAM-1 levels were decreased at week 2 of both cycles (P values < 0.01). sICAM-1 levels were elevated, however, at the start of cycle 4 as compared with pretreatment (P < 0.01). Chemotherapy led to an increase in sICAM-1 levels in node-positive but not node-negative patients (P < 0.01). VEGF levels were decreased at week 2 of cycle 4 (P = 0.001) and remained so at week 3. Similar to sICAM-1, VEGF levels were elevated at the start of cycle 4 as compared with pretreatment (P < 0.006). Soluble P-selectin levels decreased during week 2 of cycle 4 (P = 0.026). Neither interleukin-6 or von Willebrand factor were significantly changed in response to chemotherapy.

Conclusions: The findings support prior studies suggesting that sICAM-1 levels derive from sources other than endothelial cells. In addition, whereas the more immediate effect of chemotherapy is to reduce sICAM-1 and VEGF, continued treatment may lead to significant elevations.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Anthracyclines / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Disease Progression
  • Endothelium, Vascular / pathology
  • Female
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis*
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / metabolism
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Metastasis
  • P-Selectin / biosynthesis
  • Prognosis
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Time Factors
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • von Willebrand Factor / biosynthesis

Substances

  • Anthracyclines
  • Interleukin-6
  • P-Selectin
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Vascular Endothelial Growth Factor A
  • von Willebrand Factor
  • Intercellular Adhesion Molecule-1