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

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. Access through your

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BEING VIEWED BY OTHERS PROSPECTIVE VALIDATION OF _VEGF_ AND _ENOS_ POLYMORPHISMS AS PREDICTORS OF FIRST-LINE BEVACIZUMAB EFFICACY IN PATIENTS WITH METASTATIC COLORECTAL CANCER Article Open

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COLORECTAL CANCER Article Open access 24 January 2022 INFLUENCE OF NOS3 RS2070744 GENOTYPES ON HEPATOCELLULAR CARCINOMA PATIENTS TREATED WITH LENVATINIB Article Open access 13 October 2020

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Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras,

Greece A K Koutras & H P Kalofonos * Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece V Kotoula & K Papadopoulou * Department of

Clinical Therapeutics, ‘Alexandra’ Hospital, University of Athens School of Medicine, Athens, Greece C Papadimitriou & F Zagouri * Department of Medical Oncology, ‘Papageorgiou’

Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece D Dionysopoulos & G Fountzilas * Department of Pathology, University Hospital of Patras, Patras,

Greece H P Kourea * Second Department of Medical Oncology, ‘Metropolitan’ Hospital, Piraeus, Greece D V Skarlos * Third Department of Medical Oncology, ‘Agii Anargiri’ Cancer Hospital,

Athens, Greece E Samantas * Second Department of Medical Oncology, Hygeia Hospital, Athens, Greece P Kosmidis * Second Department of Internal Medicine, Oncology Section, ‘Hippokration’

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ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 25 May 2013 * Revised: 03 August 2013 * Accepted:

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initiative KEYWORDS * breast cancer * clinical outcome * polymorphisms * vascular endothelial growth factor * weekly docetaxel