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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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Cancers
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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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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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