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12.07.2018 | Clinical trial | Ausgabe 1/2018

Breast Cancer Research and Treatment 1/2018

The clinical relevance of serum vascular endothelial growth factor (VEGF) in correlation to circulating tumor cells and other serum biomarkers in patients with metastatic breast cancer

Breast Cancer Research and Treatment > Ausgabe 1/2018
Malgorzata Banys-Paluchowski, Isabell Witzel, Sabine Riethdorf, Klaus Pantel, Brigitte Rack, Wolfgang Janni, Peter A. Fasching, Bahriye Aktas, Sabine Kasimir-Bauer, Andreas Hartkopf, Erich-Franz Solomayer, Tanja Fehm, Volkmar Müller
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s10549-018-4882-z) contains supplementary material, which is available to authorized users.
This study was conducted on behalf of the DETECT Study Group.



VEGF is one of the most important angiogenesis-stimulating cytokines and has been previously shown to be overexpressed in several solid cancers. The aim of the present study was to assess the clinical relevance of serum VEGF (sVEGF) in a large cohort of metastatic breast cancer patients and to explore the relationship between sVEGF and other blood-based biomarkers.


Two hundred fifty-three patients with metastatic breast cancer were enrolled in this prospective, multicentre study. Blood samples were collected before start of first-line or later-line treatment. sVEGF was quantified by a commercially available ELISA. Circulating tumor cells (CTCs) were detected using CellSearch and other biomarkers (EGFR, HER2, RAS p21, TIMP1, CAIX) by ELISA.


Levels of sVEGF were determined in all patients, with a median concentration of 231 pg/ml. After a median follow-up of 19 months, median overall survival (OS) was 10.2 months in patients with sVEGF levels above the upper quartile (i.e. 367 pg/ml), while median OS has not been reached in patients with sVEGF < 367 pg/ml (p < 0.001). Median progression-free survival (PFS) was 4.8 months for patients with sVEGF ≥ 367 pg/ml versus 9.1 months with sVEGF levels < 367 pg/ml (p < 0.001). Patients with sVEGF levels ≥ 367 pg/ml and ≥ 5 CTCs had the shortest OS, while those with sVEGF < 367 pg/ml and non-elevated CTCs had the longest OS. CTCs, grading, line of therapy and RAS p21 were independent predictors of OS. sVEGF, line of therapy and CTCs were independent predictors of PFS in the multivariate analysis.


Metastatic breast cancer patients with elevated levels of sVEGF have significantly worse clinical outcome. This finding supports the biological role of VEGF in breast cancer. Trial registration: Current Controlled Trials ISRCTN59722891 (DETECT).

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