Genetic variants in VEGF pathway genes in neoadjuvant breast cancer patients receiving bevacizumab: Results from the randomized phase III GeparQuinto study

Alexander Hein, Diether Lambrechts, Gunter Von Minckwitz, Lothar Häberle, Holger Eidtmann, Hans Tesch, Michael Untch, Jörn Hilfrich, Christian Schem, Mahdi Rezai, Bernd Gerber, Serban Dan Costa, Jens Uwe Blohmer, Kathrin Schwedler, Kornelia Kittel, Tanja Fehm, Georg Kunz, Matthias W. Beckmann, Arif B. Ekici, Claus HanuschJens Huober, Cornelia Liedtke, Christine Mau, Matthieu Moisse, Volkmar Müller, Valentina Nekljudova, Gilian Peuteman, Brigitte Rack, Matthias Rübner, Thomas Van Brussel, Liewei Wang, Richard M. Weinshilboum, Sibylle Loibl, Peter A. Fasching

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Studies assessing the effect of bevacizumab (BEV) on breast cancer (BC) outcome have shown different effects on progression-free and overall survival, suggesting that a subgroup of patients may benefit from this treatment. Unfortunately, no biomarkers exist to identify these patients. Here, we investigate whether single nucleotide polymorphisms (SNPs) in VEGF pathway genes correlate with pathological complete response (pCR) in the neoadjuvant GeparQuinto trial. HER2-negative patients were randomized into treatment arms receiving either BEV combined with standard chemotherapy or chemotherapy alone. In a pre-planned biomarker study, DNA was collected from 729 and 724 patients, respectively from both treatment arms, and genotyped for 125 SNPs. Logistic regression assessed interaction between individual SNPs and both treatment arms to predict pCR. Five SNPs may be associated with a better response to BEV, but none of them remained significant after correction for multiple testing. The two SNPs most strongly associated, rs833058 and rs699947, were located upstream of the VEGF-A promoter. Odds ratios for the homozygous common, heterozygous and homozygous rare rs833058 genotypes were 2.36 (95% CI, 1.49-3.75), 1.20 (95% CI, 0.88-1.64) and 0.61 (95% CI, 0.34-1.12). Notably, some SNPs in VEGF-A exhibited a more pronounced effect in the triple-negative subgroup. Several SNPs in VEGF-A may be associated with improved pCR when receiving BEV in the neoadjuvant setting. Although none of the observed effects survived correction for multiple testing, our observations are consistent with previous studies on BEV efficacy in BC. Further research is warranted to clarify the predictive value of these markers.

Original languageEnglish (US)
Pages (from-to)2981-2988
Number of pages8
JournalInternational Journal of Cancer
Volume137
Issue number12
DOIs
StatePublished - Dec 15 2015

Keywords

  • SNP
  • VEGF
  • anti-angiogenesis
  • bevacizumab
  • biomarker
  • breast cancer
  • genetic variant
  • prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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