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

Publication

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

Journal Paper/Review - Jul 6, 2015

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

Citation

Hein A, Ekici A, Hanusch C, Huober J, Liedtke C, Mau C, Moisse M, Müller V, Nekljudova V, Peuteman G, Rack B, Rübner M, Van Brussel T, Wang L, Weinshilboum R, Loibl S, Beckmann M, Kunz G, Lambrechts D, von Minckwitz G, Häberle L, Eidtmann H, Tesch H, Untch M, Hilfrich J, Schem C, Rezai M, Gerber B, Dan Costa S, Blohmer J, Schwedler K, Kittel K, Fehm T, Fasching P. Genetic variants in VEGF pathway genes in neoadjuvant breast cancer patients receiving bevacizumab: Results from the randomized phase III GeparQuinto study. Int J Cancer 2015; 137:2981-8.

Type

Journal Paper/Review (English)

Journal

Int J Cancer 2015; 137

Publication Date

Jul 6, 2015

Issn Electronic

1097-0215

Pages

2981-8

Brief description/objective

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.