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

Background:

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 this study was to examine the clinical relevance of serum VEGF (sVEGF) and circulating tumor cells (CTCs) in metastatic breast cancer.

Methods:

253 patients were enrolled in this prospective multicentre study. Blood samples were collected before the start of a new line of treatment and sVEGF was quantified by a commercially available ELISA. CTCs were detected using CellSearch.

Results:

Median sVEGF concentration was 231pg/ml. No association was found between sVEGF and CTCs. Mean sVEGF levels in patients treated previously with bevacizumab were significantly higher than in untreated patients. After a median follow up of 19 months, patients with elevated sVEGF had significantly shorter OS and PFS than those with non-elevated levels (median OS: 10.2 months versus not reached, p < 0.001; median PFS: 9.1 versus 4.8 months, p < 0.001). Patients with sVEGF levels ≥367pg/ml and ≥5 CTCs/7.5 ml blood had the shortest OS, followed by those with elevated CTCs and sVEGF< 367pg/ml and patients with < 5 CTCs and sVEGF≥367pg/ml, while those with sVEGF< 367pg/ml and non-elevated CTCs had the longest OS. Presence of ≥5 CTCs, higher grading and higher line of therapy were independent predictors of shorter OS. sVEGF≥367pg/ml, higher line of therapy and elevated CTC counts were independent predictors of shorter PFS.

Conclusions:

Metastatic breast cancer patients with elevated sVEGF levels show an impaired clinical outcome. Our findings support the biologic role of VEGF in breast cancer.