Vascular endothelial growth factor independently predicts the efficacy of postoperative radiotherapy in node-negative breast cancer patients.
OBJECTIVE
Vascular endothelial growth factor (VEGF) is a mediator of angiogenesis and is up-regulated under hypoxic conditions. Hypoxic tumors are known to exhibit resistance to radiotherapy. We investigated the association between VEGF levels in tumor tissue and the effect of radiotherapy for relapse-free survival (RFS) and overall survival (OS) in node-negative breast cancer.


METHODS
The study was performed on 489 patients; 221 patients received postoperative radiotherapy as part of the breast-conserving therapy (BCT), and 268 patients were treated by mastectomy only. VEGF levels were measured using a quantitative ELISA. None of the patients received adjuvant systemic therapy. The median follow-up was 64 months (range, 2-149) after BCT and 59 months (range, 2-117) after mastectomy. Correlations with well-known prognostic factors were studied, and univariate and multivariate survival analyses were performed.


RESULTS
Only in the BCT group, high VEGF levels (equal or above the median level) predicted a reduced RFS and OS in univariate survival analysis (P = 0.004 and P = 0.028, respectively), implying that patients with high VEGF levels have less benefit from BCT. This was seen as a significant interaction between local treatment and VEGF for the total population for RFS (P = 0.012) and OS (P = 0.004). The interaction between local treatment and tumor size was also significant for both RFS (P = 0.046) and OS (P = 0.019) in the multivariate analysis.


CONCLUSIONS
These results show that, in node-negative patients, both tumor size and VEGF content predict for a reduced efficacy of postoperative radiotherapy as part of BCT, indicating that the choice of local treatment of these patients can also be modified based on tumor VEGF content.
Manders
Peggy
P
Department of Chemical Endocrinology, University Medical Centre Nijmegen, Nijmegen, The Netherlands. p.manders@ace.umcn.nl
Sweep
Fred C G J
FC
Tjan-Heijnen
Vivianne C G
VC
Geurts-Moespot
Anneke
A
van Tienoven
Doorléne T H
DT
Foekens
John A
JA
Span
Paul N
PN
Bussink
Jan
J
Beex
Louk V A M
LV
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000532:radiotherapy*; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D000860:Hypoxia; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D011379:Prognosis; D016016:Proportional Hazards Models; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D042461:Vascular Endothelial Growth Factor A