title: MMP2 and MMP9 serum levels are associated with favorable outcome in patients with inflammatory breast cancer treated with bevacizumab-based neoadjuvant chemotherapy in the BEVERLY-2 study.
abstract: OBJECTIVE
  Addition of bevacizumab to trastuzumab-based neoadjuvant chemotherapy in HER2-positive inflammatory breast cancer (IBC) was associated with favorable outcome in the BEVERLY-2 phase II trial. Circulating levels of matrix metalloproteinases (MMP) 2 and 9 were correlated to high response rate and prolonged survival in high-grade glioma treated with bevacizumab. We examined the prognostic impact of MMP2 and MMP9 serum levels in BEVERLY-2 patients.
  
  
  METHODS
  MMP2 and MMP9 serum levels were assessed using ELISA at baseline and before surgery in 45/52 available samples. Correlations were tested with pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS).
  
  
  RESULTS
  Baseline (b) MMP2 and MMP9 serum levels were independent from patient characteristics and circulating tumor or endothelial cells, and were not correlated to pCR. High bMMP2 was correlated to better DFS (p=0.001) and OS (p=0.032), while low bMMP9 was correlated to better OS (p=0.022) and tended to be associated with longer DFS (p=0.071). In multivariate analyses, bMMP2 (p=0.003, Hazard Ratio [HR]: 0.115) and bMMP9 (p=0.041, HR: 3.511) remained correlated to DFS. As continuous variables, bMMP2 was associated with relapse (p=0.002) and death (p=0.049), while bMMP9 was associated with death (p=0.035). During treatment, significant increase in MMP2 and decrease in MMP9 levels (p<0.001 for both) were observed in 100% and 87% of patients respectively.
  
  
  CONCLUSIONS
  High bMMP2 and low bMMP9 serum levels were associated with better survival in HER2-positive IBC patients treated with bevacizumab- and trastuzumab-based neoadjuvant chemotherapy. Their predictive value of bevacizumab benefit should be evaluated in a randomized trial.
authors.affiliation: Institut Paoli-Calmettes, Medical Oncology Department, Marseille, France.|CRO2, Neuro-Oncology Department, UMRS_911, Marseille, France.|APHM, Marseille, France.|Aix-Marseille University, Marseille, France.
authors.forename: Emeline
authors.initials: E
authors.lastname: Tabouret
authors.affiliation: Institut Paoli-Calmettes, Medical Oncology Department, Marseille, France.|Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France.|Centre de Recherche en Cancérologie de Marseille, CNRS, Marseille, France.|Aix-Marseille University, Marseille, France.
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.affiliation: Institut Curie & Université Paris Descartes, Medical Oncology Department, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Pierga
authors.affiliation: Centre Paul Strauss, Medical Oncology Department, Strasbourg, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Petit
authors.affiliation: Centre François Baclesse, Medical Oncology Department, Caen, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Levy
authors.affiliation: Centre Antoine Lacassagne, Medical Oncology Department, Nice, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Ferrero
authors.affiliation: Centre René Gauducheau, Medical Oncology Department, Saint-Herblin, France.
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.affiliation: APHP-Tenon, APREC, Paris, France.|IUC-UPMC, Sorbonne University, Paris, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gligorov
authors.affiliation: Hopital Rene Huguenin-Institut Curie, Medical Oncology Department, Saint-Cloud, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Lerebours
authors.affiliation: Institut Claudius Regaud, Medical Oncology Department, Toulouse, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Roché
authors.affiliation: Institut Leon Berard, Medical Oncology Department, Lyon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.affiliation: Translational Cancer Research Unit, GZA Hospitals Sint-Augustinus, Wilrijk, Belgium.|Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.|Department of Oncology, KU Leuven, Leuven, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: van Laere
authors.affiliation: The University of Texas MD Anderson Cancer Center, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Houston, TX, USA.
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France.|Centre de Recherche en Cancérologie de Marseille, CNRS, Marseille, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Toiron
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France.|Centre de Recherche en Cancérologie de Marseille, CNRS, Marseille, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Borg
authors.affiliation: Institut Paoli-Calmettes, Medical Oncology Department, Marseille, France.|Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France.|Centre de Recherche en Cancérologie de Marseille, CNRS, Marseille, France.|Aix-Marseille University, Marseille, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.affiliation: CRO2, Neuro-Oncology Department, UMRS_911, Marseille, France.|APHM, Marseille, France.|Centre de Recherche en Cancérologie de Marseille, CNRS, Marseille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Chinot
authors.affiliation: Institut Paoli-Calmettes, Medical Oncology Department, Marseille, France.|Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France.|Centre de Recherche en Cancérologie de Marseille, CNRS, Marseille, France.|Aix-Marseille University, Marseille, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Gonçalves
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: bevacizumab; biomarker; inflammatory breast cancer; matrix metalloproteinase 2; matrix metalloproteinase 9