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Vascular Endothelial Growth Factor in Predicting Outcome in Breast Cancer

Department of Internal Medicine, Division of Oncology

Wilfried Renner

Clinical Institute for Medical and Chemical Laboratory Diagnostics

Herwig Köppel

Department of Internal Medicine, Division of Angiology, Medical University Graz, Graz, Austria

To the editor:

We have read with great interest the work by Konecny et al. about HER-2/neu and vascular endothelial growth factor (VEGF) expression and breast cancer outcome (1) . As we reported recently, a polymorphism downstream of the VEGF gene, 936C>T, was associated with VEGF expression and breast cancer risk (2) . Encouraged by the data of Konecny et al., we have retrieved data on metastasis in the 500 breast cancer patients from our study and performed a retrospective analysis of metastasis-free survival time. A Cox regression model, including VEGF 936T carriage, age at diagnosis, primary presence of regional lymph node metastasis, primary tumor size larger than 2 cm, and estrogen and/or progesterone receptor negativity in the primary tumor, was used to estimate the effect of the VEGF genotype on metastasis-free survival time. The study was performed according to the Austrian Gene Technology Act and has been approved by the Ethical Committee of the Medical University Graz. Written informed consent was obtained from all participating subjects. All subjects were Caucasian.

At the time of diagnoses, patients were between 28 and 84 years of age, with a mean age of 57 ± 11 years. Median time to metastasis was 34 months. Genotype frequencies were 82.4% (CC), 15.8% (CT) and 1.8% (TT). In a subgroup of 210 patients with low-grade breast cancer (histologic grade 1 or 2), 77 patients developed metastases in the time between diagnosis and study entry. The VEGF 936-T allele was protective against metastasis (Fig. 1) , showing a relative risk of 0.52 (95% confidence interval, 0.28–0.99; P = 0.046) for carriers of a VEGF 936-T allele compared with noncarriers. This effect was not seen in patients with high-grade breast cancer (relative risk, 1.07; 95% confidence interval, 0.65–1.76; P = 0.79).

View larger version (19K): [in this window] [in a new window] [Download PPT slide]   Fig. 1. VEGF 936C>T gene polymorphism and metastasis-free survival time of breast cancer patients.

We believe that these data complement the results of Konecny et al. and expand the knowledge about genetic determinants of breast cancer progression and metastasis. If our observations can be reproduced in prospective studies, the VEGF 936C>T genotype may serve as an additional prognostic marker for breast cancer metastases. Additionally, it might be interesting to evaluate the potential role of this polymorphism for pharmacogenetics of VEGF-targeted molecular therapies, e.g., Bevacizumab.

REFERENCES

1. Konecny GE, Meng YG, Untch M, et al Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. Clin Cancer Res 2004;10:1706-16.[Abstract/Free Full Text]
2. Krippl P, Langsenlehner U, Renner W, et al A common 936 C/T gene polymorphism of vascular endothelial growth factor is associated with decreased breast cancer risk. Int J Cancer 2003;106:468-71.[CrossRef][Medline]
3. Renner W, Kotschan S, Hoffmann C, Obermayer-Pietsch B, Pilger E. A common 936 C/T mutation in the gene for vascular endothelial growth factor is associated with vascular endothelial growth factor plasma levels. J Vasc Res 2000;37:443-8.[CrossRef][Medline]

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