title: The prognostic value of vascular endothelial growth factor in 574 node-negative breast cancer patients who did not receive adjuvant systemic therapy.
abstract: The growth and metastasising capacity of solid tumours are dependent on angiogenesis. Vascular endothelial growth factor is a mediator of angiogenesis. In this study we investigated whether vascular endothelial growth factor is associated with the natural course of the disease in primary invasive breast cancer. In 574 tumours of patients with node-negative invasive breast cancer the cytosolic levels of vascular endothelial growth factor were measured using a quantitative enzyme-linked immunosorbent assay. These patients did not receive adjuvant systemic therapy and were followed for a median follow-up time of 61 months (range 2-155 months) after the primary diagnosis. Correlations with well-known prognostic factors, and univariate and multivariate survival analyses were performed. Vascular endothelial growth factor level was positively associated with age and tumour size (P=0.042 and P=0.029, respectively). In addition, vascular endothelial growth factor level was inversely, but weakly correlated with progesterone receptor levels (PgR) (r(s)=-0.090, P=0.035). A high vascular endothelial growth factor level (equal or above the median level of 0.53 ng mg(-1) protein) predicted a reduced relapse-free survival and overall survival in the univariate survival rate analysis (for both P=0.005). In the multivariate analysis as well, vascular endothelial growth factor showed to be an independent predictor of poor relapse-free survival and overall survival (P=0.045 and P=0.029, respectively), in addition to age, tumour size and PgR. The results show that cytosolic levels of vascular endothelial growth factor in tumour tissue samples are independently indicative of prognosis for patients with node-negative breast cancer who were not treated with adjuvant systemic therapy. This implies that vascular endothelial growth factor is related with the natural course of breast cancer progression.
authors.affiliation: Department of Medical Oncology, University Medical Centre Nijmegen, Nijmegen, The Netherlands. p.manders@ace.azn.nl
authors.forename: P
authors.initials: P
authors.lastname: Manders
authors.forename: L V A M
authors.initials: LV
authors.lastname: Beex
authors.forename: V C G
authors.initials: VC
authors.lastname: Tjan-Heijnen
authors.forename: J
authors.initials: J
authors.lastname: Geurts-Moespot
authors.forename: T H
authors.initials: TH
authors.lastname: Van Tienoven
authors.forename: J A
authors.initials: JA
authors.lastname: Foekens
authors.forename: C G J
authors.initials: CG
authors.lastname: Sweep
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D016228:Endothelial Growth Factors / Q000032:analysis*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis*; D008222:Lymphokines / Q000032:analysis*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D021701:Sentinel Lymph Node Biopsy; D016019:Survival Analysis; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors