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

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Genetic variants in VEGF pathway genes in neoadjuvant breast cancer patients receiving bevacizumab: Results from the randomized phase III GeparQuinto study. / Hein, Alexander; 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; Kunz, Georg; Beckmann, Matthias W; 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; Fasching, Peter A.

in: INT J CANCER, Jahrgang 137, Nr. 12, 15.12.2015, S. 2981-8.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Hein, A, 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-U, Schwedler, K, Kittel, K, Fehm, T, Kunz, G, Beckmann, MW, Ekici, AB, 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, RM, Loibl, S & Fasching, PA 2015, 'Genetic variants in VEGF pathway genes in neoadjuvant breast cancer patients receiving bevacizumab: Results from the randomized phase III GeparQuinto study', INT J CANCER, Jg. 137, Nr. 12, S. 2981-8. https://doi.org/10.1002/ijc.29656

APA

Hein, A., 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-U., Schwedler, K., Kittel, K., Fehm, T., Kunz, G., Beckmann, M. W., Ekici, A. B., ... Fasching, P. A. (2015). Genetic variants in VEGF pathway genes in neoadjuvant breast cancer patients receiving bevacizumab: Results from the randomized phase III GeparQuinto study. INT J CANCER, 137(12), 2981-8. https://doi.org/10.1002/ijc.29656

Vancouver

Hein A, Lambrechts D, von Minckwitz G, Häberle L, Eidtmann H, Tesch H et al. 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 Dez 15;137(12):2981-8. https://doi.org/10.1002/ijc.29656

Bibtex

@article{070333065a4a4576bdee25f9743f1522,
title = "Genetic variants in VEGF pathway genes in neoadjuvant breast cancer patients receiving bevacizumab: Results from the randomized phase III GeparQuinto study",
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.",
author = "Alexander Hein and Diether Lambrechts and {von Minckwitz}, Gunter and Lothar H{\"a}berle and Holger Eidtmann and Hans Tesch and Michael Untch and J{\"o}rn Hilfrich and Christian Schem and Mahdi Rezai and Bernd Gerber and {Dan Costa}, Serban and Jens-Uwe Blohmer and Kathrin Schwedler and Kornelia Kittel and Tanja Fehm and Georg Kunz and Beckmann, {Matthias W} and Ekici, {Arif B} and Claus Hanusch and Jens Huober and Cornelia Liedtke and Christine Mau and Matthieu Moisse and Volkmar M{\"u}ller and Valentina Nekljudova and Gilian Peuteman and Brigitte Rack and Matthias R{\"u}bner and {Van Brussel}, Thomas and Liewei Wang and Weinshilboum, {Richard M} and Sibylle Loibl and Fasching, {Peter A}",
note = "{\textcopyright} 2015 UICC.",
year = "2015",
month = dec,
day = "15",
doi = "10.1002/ijc.29656",
language = "English",
volume = "137",
pages = "2981--8",
journal = "INT J CANCER",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "12",

}

RIS

TY - JOUR

T1 - Genetic variants in VEGF pathway genes in neoadjuvant breast cancer patients receiving bevacizumab: Results from the randomized phase III GeparQuinto study

AU - Hein, Alexander

AU - Lambrechts, Diether

AU - von Minckwitz, Gunter

AU - Häberle, Lothar

AU - Eidtmann, Holger

AU - Tesch, Hans

AU - Untch, Michael

AU - Hilfrich, Jörn

AU - Schem, Christian

AU - Rezai, Mahdi

AU - Gerber, Bernd

AU - Dan Costa, Serban

AU - Blohmer, Jens-Uwe

AU - Schwedler, Kathrin

AU - Kittel, Kornelia

AU - Fehm, Tanja

AU - Kunz, Georg

AU - Beckmann, Matthias W

AU - Ekici, Arif B

AU - Hanusch, Claus

AU - Huober, Jens

AU - Liedtke, Cornelia

AU - Mau, Christine

AU - Moisse, Matthieu

AU - Müller, Volkmar

AU - Nekljudova, Valentina

AU - Peuteman, Gilian

AU - Rack, Brigitte

AU - Rübner, Matthias

AU - Van Brussel, Thomas

AU - Wang, Liewei

AU - Weinshilboum, Richard M

AU - Loibl, Sibylle

AU - Fasching, Peter A

N1 - © 2015 UICC.

PY - 2015/12/15

Y1 - 2015/12/15

N2 - 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.

AB - 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.

U2 - 10.1002/ijc.29656

DO - 10.1002/ijc.29656

M3 - SCORING: Journal article

C2 - 26100253

VL - 137

SP - 2981

EP - 2988

JO - INT J CANCER

JF - INT J CANCER

SN - 0020-7136

IS - 12

ER -