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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

1
Epidemiology and Biostatistics Department, Centre Antoine Lacassagne, University Côte d’Azur, 06100 Nice, France
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Cancer Pharmacogenetics and Radiogenetics Unit (UPRC) 7497, Centre Antoine Lacassagne, University Côte d’Azur, 33 avenue de Valombrose, 06100 Nice, France
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Scientific Research National Center (CNRS), Inserm, Ircan, FHU-Oncoage, Centre Antoine Lacassagne, University Côte d’Azur, 06100 Nice, France
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Oncopharmacology Unit, Centre Antoine Lacassagne, University Côte d’Azur, 06100 Nice, France
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Department of Biostatistics, Institut Claudius Regaud, IUCT Oncopole, 31300 Toulouse, France
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Medical Oncology Department, Institut Curie, St Cloud, 92210 Paris, France
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Medical Oncology Department, Centre Val d’Aurelle-Paul Lamarque, 34298 Montpellier, France
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Medical Oncology Department, Centre Georges François Leclerc, 2100 Dijon, France
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Medical Oncology Department, Institut Paoli-Calmettes, 13900 Marseille, France
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Medical Oncology Department, Centre Antoine Lacassagne, University Côte d’Azur, 06100 Nice, France
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Medical Oncology Department, Institut Bergonie, 33000 Bordeaux, France
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Medical Oncology Department, Centre Leon Berard, 69008 Lyon, France
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Oncology Department, S. Croce & Carle Teaching Hospital, 12100 Cuneo, Italy
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Research & Development Departement, Unicancer, 94270 Paris, France
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Department of Medical Oncology, Paris University, 70006 Paris, France
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(11), 414; https://doi.org/10.3390/ph13110414
Received: 20 October 2020 / Revised: 17 November 2020 / Accepted: 18 November 2020 / Published: 23 November 2020
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. View Full-Text
Keywords: breast cancer; precision medicine; pharmacogenetics; bevacizumab; SNP; VEGF; overall survival breast cancer; precision medicine; pharmacogenetics; bevacizumab; SNP; VEGF; overall survival
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Figure 1

MDPI and ACS Style

Gal, J.; Milano, G.; Brest, P.; Ebran, N.; Gilhodes, J.; Llorca, L.; Dubot, C.; Romieu, G.; Desmoulins, I.; Brain, E.; Goncalves, A.; Ferrero, J.-M.; Cottu, P.-H.; Debled, M.; Tredan, O.; Chamorey, E.; Merlano, M.C.; Lemonnier, J.; Etienne-Grimaldi, M.-C.; Pierga, J.-Y. 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. Pharmaceuticals 2020, 13, 414. https://doi.org/10.3390/ph13110414

AMA Style

Gal J, Milano G, Brest P, Ebran N, Gilhodes J, Llorca L, Dubot C, Romieu G, Desmoulins I, Brain E, Goncalves A, Ferrero J-M, Cottu P-H, Debled M, Tredan O, Chamorey E, Merlano MC, Lemonnier J, Etienne-Grimaldi M-C, Pierga J-Y. 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. Pharmaceuticals. 2020; 13(11):414. https://doi.org/10.3390/ph13110414

Chicago/Turabian Style

Gal, Jocelyn, Gérard Milano, Patrick Brest, Nathalie Ebran, Julia Gilhodes, Laurence Llorca, Coraline Dubot, Gilles Romieu, Isabelle Desmoulins, Etienne Brain, Anthony Goncalves, Jean-Marc Ferrero, Paul-Henri Cottu, Marc Debled, Olivier Tredan, Emmanuel Chamorey, Marco C. Merlano, Jérôme Lemonnier, Marie-Christine Etienne-Grimaldi, and Jean-Yves Pierga. 2020. "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" Pharmaceuticals 13, no. 11: 414. https://doi.org/10.3390/ph13110414

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