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VEGF-Related Germinal Polymorphisms May Identify a Subgroup of Breast Cancer Patients with Favorable Outcome under Bevacizumab-Based Therapy—A Message from COMET, a French Unicancer Multicentric Study

The prospective multicenter COMET trial followed a cohort of 306 consecutive metastatic breast cancer patients receiving bevacizumab and paclitaxel as first-line chemotherapy. This study was intended to identify and validate reliable biomarkers to better predict bevacizumab treatment outcomes and al...

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Autores principales: Gal, Jocelyn, Milano, Gérard, Brest, Patrick, Ebran, Nathalie, Gilhodes, Julia, Llorca, Laurence, Dubot, Coraline, Romieu, Gilles, Desmoulins, Isabelle, Brain, Etienne, Goncalves, Anthony, Ferrero, Jean-Marc, Cottu, Paul-Henri, Debled, Marc, Tredan, Olivier, Chamorey, Emmanuel, Merlano, Marco Carlo, Lemonnier, Jérôme, Etienne-Grimaldi, Marie-Christine, Pierga, Jean-Yves
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700430/
https://www.ncbi.nlm.nih.gov/pubmed/33238394
http://dx.doi.org/10.3390/ph13110414
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author Gal, Jocelyn
Milano, Gérard
Brest, Patrick
Ebran, Nathalie
Gilhodes, Julia
Llorca, Laurence
Dubot, Coraline
Romieu, Gilles
Desmoulins, Isabelle
Brain, Etienne
Goncalves, Anthony
Ferrero, Jean-Marc
Cottu, Paul-Henri
Debled, Marc
Tredan, Olivier
Chamorey, Emmanuel
Merlano, Marco Carlo
Lemonnier, Jérôme
Etienne-Grimaldi, Marie-Christine
Pierga, Jean-Yves
author_facet Gal, Jocelyn
Milano, Gérard
Brest, Patrick
Ebran, Nathalie
Gilhodes, Julia
Llorca, Laurence
Dubot, Coraline
Romieu, Gilles
Desmoulins, Isabelle
Brain, Etienne
Goncalves, Anthony
Ferrero, Jean-Marc
Cottu, Paul-Henri
Debled, Marc
Tredan, Olivier
Chamorey, Emmanuel
Merlano, Marco Carlo
Lemonnier, Jérôme
Etienne-Grimaldi, Marie-Christine
Pierga, Jean-Yves
author_sort Gal, Jocelyn
collection PubMed
description The prospective multicenter COMET trial followed a cohort of 306 consecutive metastatic breast cancer patients receiving bevacizumab and paclitaxel as first-line chemotherapy. This study was intended to identify and validate reliable biomarkers to better predict bevacizumab treatment outcomes and allow for a more personalized use of this antiangiogenic agent. To that end, we aimed to establish risk scores for survival prognosis dichotomization based on classic clinico-pathological criteria combined or not with single nucleotide polymorphisms (SNPs). The genomic DNA of 306 patients was extracted and a panel of 13 SNPs, covering seven genes previously documented to be potentially involved in drug response, were analyzed by means of high-throughput genotyping. In receiver operating characteristic (ROC) analyses, the hazard model based on a triple-negative cancer phenotype variable, combined with specific SNPs in VEGFA (rs833061), VEGFR1 (rs9582036) and VEGFR2 (rs1870377), had the highest predictive value. The overall survival hazard ratio of patients assigned to the poor prognosis group based on this model was 3.21 (95% CI (2.33–4.42); p < 0.001). We propose that combining this pharmacogenetic approach with classical clinico-pathological characteristics could markedly improve clinical decision-making for breast cancer patients receiving bevacizumab-based therapy.
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spelling pubmed-77004302020-11-30 VEGF-Related Germinal Polymorphisms May Identify a Subgroup of Breast Cancer Patients with Favorable Outcome under Bevacizumab-Based Therapy—A Message from COMET, a French Unicancer Multicentric Study Gal, Jocelyn Milano, Gérard Brest, Patrick Ebran, Nathalie Gilhodes, Julia Llorca, Laurence Dubot, Coraline Romieu, Gilles Desmoulins, Isabelle Brain, Etienne Goncalves, Anthony Ferrero, Jean-Marc Cottu, Paul-Henri Debled, Marc Tredan, Olivier Chamorey, Emmanuel Merlano, Marco Carlo Lemonnier, Jérôme Etienne-Grimaldi, Marie-Christine Pierga, Jean-Yves Pharmaceuticals (Basel) Article The prospective multicenter COMET trial followed a cohort of 306 consecutive metastatic breast cancer patients receiving bevacizumab and paclitaxel as first-line chemotherapy. This study was intended to identify and validate reliable biomarkers to better predict bevacizumab treatment outcomes and allow for a more personalized use of this antiangiogenic agent. To that end, we aimed to establish risk scores for survival prognosis dichotomization based on classic clinico-pathological criteria combined or not with single nucleotide polymorphisms (SNPs). The genomic DNA of 306 patients was extracted and a panel of 13 SNPs, covering seven genes previously documented to be potentially involved in drug response, were analyzed by means of high-throughput genotyping. In receiver operating characteristic (ROC) analyses, the hazard model based on a triple-negative cancer phenotype variable, combined with specific SNPs in VEGFA (rs833061), VEGFR1 (rs9582036) and VEGFR2 (rs1870377), had the highest predictive value. The overall survival hazard ratio of patients assigned to the poor prognosis group based on this model was 3.21 (95% CI (2.33–4.42); p < 0.001). We propose that combining this pharmacogenetic approach with classical clinico-pathological characteristics could markedly improve clinical decision-making for breast cancer patients receiving bevacizumab-based therapy. MDPI 2020-11-23 /pmc/articles/PMC7700430/ /pubmed/33238394 http://dx.doi.org/10.3390/ph13110414 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gal, Jocelyn
Milano, Gérard
Brest, Patrick
Ebran, Nathalie
Gilhodes, Julia
Llorca, Laurence
Dubot, Coraline
Romieu, Gilles
Desmoulins, Isabelle
Brain, Etienne
Goncalves, Anthony
Ferrero, Jean-Marc
Cottu, Paul-Henri
Debled, Marc
Tredan, Olivier
Chamorey, Emmanuel
Merlano, Marco Carlo
Lemonnier, Jérôme
Etienne-Grimaldi, Marie-Christine
Pierga, Jean-Yves
VEGF-Related Germinal Polymorphisms May Identify a Subgroup of Breast Cancer Patients with Favorable Outcome under Bevacizumab-Based Therapy—A Message from COMET, a French Unicancer Multicentric Study
title VEGF-Related Germinal Polymorphisms May Identify a Subgroup of Breast Cancer Patients with Favorable Outcome under Bevacizumab-Based Therapy—A Message from COMET, a French Unicancer Multicentric Study
title_full VEGF-Related Germinal Polymorphisms May Identify a Subgroup of Breast Cancer Patients with Favorable Outcome under Bevacizumab-Based Therapy—A Message from COMET, a French Unicancer Multicentric Study
title_fullStr VEGF-Related Germinal Polymorphisms May Identify a Subgroup of Breast Cancer Patients with Favorable Outcome under Bevacizumab-Based Therapy—A Message from COMET, a French Unicancer Multicentric Study
title_full_unstemmed VEGF-Related Germinal Polymorphisms May Identify a Subgroup of Breast Cancer Patients with Favorable Outcome under Bevacizumab-Based Therapy—A Message from COMET, a French Unicancer Multicentric Study
title_short VEGF-Related Germinal Polymorphisms May Identify a Subgroup of Breast Cancer Patients with Favorable Outcome under Bevacizumab-Based Therapy—A Message from COMET, a French Unicancer Multicentric Study
title_sort vegf-related germinal polymorphisms may identify a subgroup of breast cancer patients with favorable outcome under bevacizumab-based therapy—a message from comet, a french unicancer multicentric study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700430/
https://www.ncbi.nlm.nih.gov/pubmed/33238394
http://dx.doi.org/10.3390/ph13110414
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