Vascular endothelial growth factor is a strong predictor of early distant recurrences in a prospective study of premenopausal women with lymph-node negative breast cancer

We investigate the prognostic significance of the pro-angiogenic cytokine vascular endothelial growth factor (VEGF), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1), and S-phase fraction (SPF) for distant disease free survival (DDFS) in 219 premenopausal patients with node-negative breast cancer (NNBC). In univariate analysis significantly shorter DDFS was observed for patients with high VEGF (p = 0.006), high uPA (p = 0.001), and high SPF (p < 0.001). The prognostic significance of VEGF varied over time being very strong for early relapses (0-2.25 years follow-up) (HR = 7.9; p = 0.006) while no difference was seen in the subsequent follow-up period (HR = 1.3; p = 0.62). In a series of bivariate analyses VEGF provided prognostic information during the whole observation period (0-72 months) in addition to age, tumour size, oestrogen receptor (ER), progesterone receptor (PgR), and uPA. Also this effect was more pronounced during the first follow-up period suggesting VEGF as a marker of early recurrences.