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Vascular endothelial growth factor polymorphisms and clinical outcome in patients with metastatic breast cancer treated with weekly docetaxel

The Pharmacogenomics Journal volume 14, pages 248–255 (2014)Cite this article

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Abstract

The aim of the study was to evaluate the association of vascular endothelial growth factor (VEGF) genotypes with treatment efficacy in a phase II trial. This study evaluated weekly docetaxel, as first-line treatment for metastatic breast cancer. Existing data from in vitro and animal model experiments suggest that docetaxel at low doses has anti-angiogenic activity. DNA was extracted from blood samples of 86 patients participating in the trial. Genotyping was performed for selected single-nucleotide polymorphisms (SNPs; VEGF−2578, −1498, −1154, and +936). Moreover, due to the highly polymorphic nature of the studied areas, we were able to analyze additional registered SNPs. All candidate genotypes were evaluated for associations with overall survival (OS), progression-free survival (PFS) and response rate. The VEGF−1154 GG genotype was more frequent in patients not responding to treatment compared with responders (42.9% vs 0.0%, P=0.048). Moreover, the VEGF−2578 AA genotype was associated with longer PFS compared with CC (hazard ratio (HR)=0.40; 95% confidence interval (CI) 0.17–0.98; pairwise P=0.0457). Patients with the VEGF−1190 GG genotype demonstrated shorter PFS compared with those with the alternative genotypes (GA and AA) combined (HR=3.85; 95% CI: 1.20–12.50; P=0.0224). In addition, the VEGF−2551/−2534 homozygous del18bp and VEGF−2430/−2425 homozygous ins1bp genotypes were associated with worse PFS compared with no deletion and no insertion, respectively (HR=2.49; 95% CI: 1.02–6.07; pairwise P=0.0442 and HR=2.57; 95% CI: 1.05–6.27; pairwise P=0.0385, respectively). Furthermore, patients with the VEGF−1498 CC genotype exhibited longer median OS compared with those with the alternatives genotypes (CT and TT) combined (HR=0.27; 95% CI: 0.08–0.89; P=0.0311). In multivariate analysis, the VEGF−2578 AA genotype retained its significance (P=0.0220) for PFS. Our results support the association of specific VEGF genotypes with clinical outcome in patients with metastatic breast cancer treated with a potentially anti-angiogenic regimen, such as weekly docetaxel. However, current results should be validated prospectively in larger cohorts.

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Authors and Affiliations

  1. Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece

    A K Koutras & H P Kalofonos

  2. Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

    V Kotoula & K Papadopoulou

  3. Department of Clinical Therapeutics, ‘Alexandra’ Hospital, University of Athens School of Medicine, Athens, Greece

    C Papadimitriou & F Zagouri

  4. Department of Medical Oncology, ‘Papageorgiou’ Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

    D Dionysopoulos & G Fountzilas

  5. Department of Pathology, University Hospital of Patras, Patras, Greece

    H P Kourea

  6. Second Department of Medical Oncology, ‘Metropolitan’ Hospital, Piraeus, Greece

    D V Skarlos

  7. Third Department of Medical Oncology, ‘Agii Anargiri’ Cancer Hospital, Athens, Greece

    E Samantas

  8. Second Department of Medical Oncology, Hygeia Hospital, Athens, Greece

    P Kosmidis

  9. Second Department of Internal Medicine, Oncology Section, ‘Hippokration’ Hospital, Athens, Greece

    D Pectasides

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  1. A K Koutras
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Correspondence to A K Koutras.

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Koutras, A., Kotoula, V., Papadimitriou, C. et al. Vascular endothelial growth factor polymorphisms and clinical outcome in patients with metastatic breast cancer treated with weekly docetaxel. Pharmacogenomics J 14, 248–255 (2014). https://doi.org/10.1038/tpj.2013.36

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