1. ¹Center for Tumor Detection and Prevention, Rorschacherstrasse 150, 9006 St Gallen, Switzerland
2. ²Senology Center of Eastern Switzerland, 9006 St Gallen, Switzerland
3. ³Biochemical Pharmacology, University of Konstanz, 78464 Konstanz, Germany
4. ⁴Internal Medicine V/Pulmonary Division, University Hospital Homburg, 66421 Homburg, Germany
5. ⁵Biotechnology Institute Thurgau, 8274 Tägerwilen, Switzerland

Correspondence: Dr G Fürstenberger, E-mail: gfuerstenberger@sg.zetup.ch

⁶These authors contributed equally to this work.

Received 26 September 2005; Revised 16 December 2005; Accepted 16 December 2005; Published online 31 January 2006.

Abstract

Circulating endothelial cells (CECs) as well as bone-marrow-derived endothelial precursor cells (EPC) play an important role in neovascularisation and tumour growth. To study the impact of neoadjuvant chemotherapy on the amounts of CEC and their precursor cells, mature CEC and their progenitors were quantified by flow cytometry in peripheral blood of breast cancer patients during anthracycline and/or taxane based neoadjuvant chemotherapy and subsequent surgery in comparison to age-matched healthy controls. Cell numbers were tested for correlation with serum levels of angiopoietin-2, erythropoietin, endostatin, endoglin, VEGF and sVCAM-1 as well as clinical and pathological features of breast cancer disease. Circulating endothelial cells were significantly elevated in breast cancer patients and decreased during chemotherapy, whereas EPC (CD34⁺/VEGFR-2⁺) as well as their progenitor cell population CD133⁺/CD34⁺ and the population of CD34⁺ stem cells increased. Concomitantly with the increase of progenitor cells an increase of VEGF, erythropoietin and angiopoietin-2 was observed. These data suggest that chemotherapy can only reduce the amounts of mature CEC, probably reflecting detached cells from tumour vessels, whereas the EPC and their progenitors are mobilised by chemotherapy. Since this mobilisation of EPC may contribute to tumour neovascularisation an early antiangiogenic therapy in combination with chemotherapy could be beneficial for the success of cancer therapy.