Early Imaging and Molecular Changes with Neoadjuvant Bevacizumab in Stage II/III Breast Cancer
This prospective, phase II study evaluated novel biomarkers as predictors of response to bevacizumab in patients with breast cancer (BC), using serial imaging methods and gene expression analysis. Patients with primary stage II/III BC received bevacizumab 15 mg/kg (cycle 1; C1), then four cycles of...
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MDPI AG
2021-07-01
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Online Access: | https://www.mdpi.com/2072-6694/13/14/3511 |
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author | José Manuel López-Vega Isabel Álvarez Antonio Antón José Juan Illarramendi Antonio Llombart Valentina Boni María José García-Velloso Josep María Martí-Climent Luis Pina Jesús García-Foncillas |
author_facet | José Manuel López-Vega Isabel Álvarez Antonio Antón José Juan Illarramendi Antonio Llombart Valentina Boni María José García-Velloso Josep María Martí-Climent Luis Pina Jesús García-Foncillas |
author_sort | José Manuel López-Vega |
collection | DOAJ |
description | This prospective, phase II study evaluated novel biomarkers as predictors of response to bevacizumab in patients with breast cancer (BC), using serial imaging methods and gene expression analysis. Patients with primary stage II/III BC received bevacizumab 15 mg/kg (cycle 1; C1), then four cycles of neoadjuvant docetaxel doxorubicin, and bevacizumab every 3 weeks (C2–C5). Tumour proliferation and hypoxic status were evaluated using <sup>18</sup>F-fluoro-3′-deoxy-3′-L-fluorothymidine (FLT)- and <sup>18</sup>F-fluoromisonidazole (FMISO)-positron emission tomography (PET) at baseline, and during C1 and C5. Pre- and post-bevacizumab vascular changes were evaluated using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Molecular biomarkers were assessed using microarray analysis. A total of 70 patients were assessed for treatment efficacy. Significant decreases from baseline in tumour proliferation (FLT-PET), vascularity, and perfusion (DCE-MRI) were observed during C1 (<i>p</i> ≤ 0.001), independent of tumour subtype. Bevacizumab treatment did not affect hypoxic tumour status (FMISO-PET). Significant changes in the expression of 28 genes were observed after C1. Changes in vascular endothelial growth factor receptor (VEGFR)-2p levels were observed in 65 patients, with a > 20% decrease in VEGFR-2p observed in 13/65. Serial imaging techniques and molecular gene profiling identified several potentially predictive biomarkers that may predict response to neoadjuvant bevacizumab therapy in BC patients. |
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issn | 2072-6694 |
language | English |
last_indexed | 2024-03-10T09:44:13Z |
publishDate | 2021-07-01 |
publisher | MDPI AG |
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series | Cancers |
spelling | doaj.art-938dfbb2a68546bd97f46277281345562023-11-22T03:24:30ZengMDPI AGCancers2072-66942021-07-011314351110.3390/cancers13143511Early Imaging and Molecular Changes with Neoadjuvant Bevacizumab in Stage II/III Breast CancerJosé Manuel López-Vega0Isabel Álvarez1Antonio Antón2José Juan Illarramendi3Antonio Llombart4Valentina Boni5María José García-Velloso6Josep María Martí-Climent7Luis Pina8Jesús García-Foncillas9Department of Medical Oncology, Marqués de Valdecilla University Hospital, 39008 Santander, SpainDepartment of Medical Oncology, University Hospital Donostia, 20080 Donostia-San Sebastián, SpainDepartment of Medical Oncology, University Hospital Miguel Servet, 50009 Zaragoza, SpainMedical Oncology Department, Complejo Hospitalario de Navarra, 31008 Pamplona, SpainDepartment of Medical Oncology, Hospital Arnau de Vilanova, 46015 Lleida, SpainSTART Madrid CIOCC, Hospital Universitario HM Sanchinarro, 28050 Madrid, SpainNuclear Medicine Department, Clínica Universidad de Navarra, 31008 Pamplona, SpainDepartment of Medical Physics and Radiation Safety, Clínica Universidad de Navarra, 31008 Pamplona, SpainDepartment of Radiology, Clínica Universidad de Navarra, 31008 Pamplona, SpainTranslational Oncology Division, OncoHealth Institute, University Hospital “Fundación Jiménez Díaz”, Autonomous University of Madrid, 28040 Madrid, SpainThis prospective, phase II study evaluated novel biomarkers as predictors of response to bevacizumab in patients with breast cancer (BC), using serial imaging methods and gene expression analysis. Patients with primary stage II/III BC received bevacizumab 15 mg/kg (cycle 1; C1), then four cycles of neoadjuvant docetaxel doxorubicin, and bevacizumab every 3 weeks (C2–C5). Tumour proliferation and hypoxic status were evaluated using <sup>18</sup>F-fluoro-3′-deoxy-3′-L-fluorothymidine (FLT)- and <sup>18</sup>F-fluoromisonidazole (FMISO)-positron emission tomography (PET) at baseline, and during C1 and C5. Pre- and post-bevacizumab vascular changes were evaluated using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Molecular biomarkers were assessed using microarray analysis. A total of 70 patients were assessed for treatment efficacy. Significant decreases from baseline in tumour proliferation (FLT-PET), vascularity, and perfusion (DCE-MRI) were observed during C1 (<i>p</i> ≤ 0.001), independent of tumour subtype. Bevacizumab treatment did not affect hypoxic tumour status (FMISO-PET). Significant changes in the expression of 28 genes were observed after C1. Changes in vascular endothelial growth factor receptor (VEGFR)-2p levels were observed in 65 patients, with a > 20% decrease in VEGFR-2p observed in 13/65. Serial imaging techniques and molecular gene profiling identified several potentially predictive biomarkers that may predict response to neoadjuvant bevacizumab therapy in BC patients.https://www.mdpi.com/2072-6694/13/14/3511bevacizumabbreast cancer biomarkersdynamic contrast-enhanced magnetic resonance imagingpositron emission tomographyvascular endothelial growth factor receptor-2 |
spellingShingle | José Manuel López-Vega Isabel Álvarez Antonio Antón José Juan Illarramendi Antonio Llombart Valentina Boni María José García-Velloso Josep María Martí-Climent Luis Pina Jesús García-Foncillas Early Imaging and Molecular Changes with Neoadjuvant Bevacizumab in Stage II/III Breast Cancer Cancers bevacizumab breast cancer biomarkers dynamic contrast-enhanced magnetic resonance imaging positron emission tomography vascular endothelial growth factor receptor-2 |
title | Early Imaging and Molecular Changes with Neoadjuvant Bevacizumab in Stage II/III Breast Cancer |
title_full | Early Imaging and Molecular Changes with Neoadjuvant Bevacizumab in Stage II/III Breast Cancer |
title_fullStr | Early Imaging and Molecular Changes with Neoadjuvant Bevacizumab in Stage II/III Breast Cancer |
title_full_unstemmed | Early Imaging and Molecular Changes with Neoadjuvant Bevacizumab in Stage II/III Breast Cancer |
title_short | Early Imaging and Molecular Changes with Neoadjuvant Bevacizumab in Stage II/III Breast Cancer |
title_sort | early imaging and molecular changes with neoadjuvant bevacizumab in stage ii iii breast cancer |
topic | bevacizumab breast cancer biomarkers dynamic contrast-enhanced magnetic resonance imaging positron emission tomography vascular endothelial growth factor receptor-2 |
url | https://www.mdpi.com/2072-6694/13/14/3511 |
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