This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Manders, P. Articles by Beex, L. V. A. M. Search for Related Content PubMed PubMed Citation Articles by Manders, P. Articles by Beex, L. V. A. M.

Vascular Endothelial Growth Factor Independently Predicts the Efficacy of Postoperative Radiotherapy in Node-Negative Breast Cancer Patients

¹ Departments of Chemical Endocrinology,
² Medical Oncology, and
³ Radiation Oncology, University Medical Centre Nijmegen, Nijmegen, and
⁴ Division of Endocrine Oncology, Department of Medical Oncology, Erasmus Medical Center–Daniel den Hoed, Rotterdam, the Netherlands

ABSTRACT

Purpose: 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.

Experimental Design: 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.

This article has been cited by other articles:

				V. Raman, D. Artemov, A. P. Pathak, P. T. Winnard Jr., S. McNutt, A. Yudina, A. Bogdanov Jr., and Z. M. Bhujwalla Characterizing Vascular Parameters in Hypoxic Regions: A Combined Magnetic Resonance and Optical Imaging Study of a Human Prostate Cancer Model. Cancer Res., October 15, 2006; 66(20): 9929 - 9936. [Abstract] [Full Text] [PDF]

				M. J. Duffy Predictive Markers in Breast and Other Cancers: A Review Clin. Chem., March 1, 2005; 51(3): 494 - 503. [Abstract] [Full Text] [PDF]

				P. N. Span, F. C.G.J. Sweep, E. T.G. Wiegerinck, V. C.G. Tjan-Heijnen, P. Manders, L. V.A.M. Beex, and J. B. de Kok Survivin Is an Independent Prognostic Marker for Risk Stratification of Breast Cancer Patients Clin. Chem., November 1, 2004; 50(11): 1986 - 1993. [Abstract] [Full Text] [PDF]