title: The dog as a naturally-occurring model for insulin-like growth factor type 1 receptor-overexpressing breast cancer: an observational cohort study.
abstract: BACKGROUND
  Dogs spontaneously develop invasive mammary carcinoma with a high prevalence of the triple-negative (TN) subtype (lack of ER-Estrogen Receptor and PR-Progesterone Receptor expression, lack of HER2-Human Epidermal Growth Factor Receptor 2 overexpression), making this animal model relevant for investigating new therapeutic pathways. Insulin-like growth factor Type-1 receptor (IGF1R) is frequently overexpressed in primary human breast cancers, with a growing role in the TN phenotype. The purpose of this study was to investigate the Dog as a candidate model for IGF1R-overexpressing mammary carcinoma.
  
  
  METHODS
  150 bitches with canine mammary carcinoma (CMC) and a known 2-year follow-up were retrospectively included. IGF1R expression was assessed by immunohistochemistry (IHC) using a similar scoring system as for HER2 in breast cancer. The prognostic value of the IGF1R expression was assessed in terms of overall and specific survival as well as disease-free interval (DFI).
  
  
  RESULTS
  47 CMC (31 %) were classified as luminal and 103 (69 %) as triple-negative (TN-CMC). 41 % of CMC overexpressed IGF1R (IHC score 3+) of which 76 % were TN-CMC and 62 % grade III. IGF1R overexpression was associated with aggressive features including lymphovascular invasion, histological grade III, low ER expression and the TN phenotype. Univariate and multivariate analyses revealed that IGF1R overexpression was associated with shorter overall and specific survivals and shorter DFI in TN-CMC.
  
  
  CONCLUSIONS
  IGF1R overexpression is common and related to a poor outcome in canine invasive mammary carcinoma, particularly in the triple negative subtype, as in human breast cancer. Preclinical studies using the Dog as a spontaneous animal model could be considered to investigate new therapies targeting IGF1R in triple-negative breast cancer.
authors.affiliation: Oniris, Université Nantes-Angers-Le Mans, Department of Human Health, Biomedical Research and Animal Models, AMaROC Unit and LDHvet laboratory, Nantes Atlantic College of Veterinary Medicine, Food Science and Engineering, Site de la Chantrerie, Route de Gachet, Nantes, F-44307, France. laetitia.jaillardon@oniris-nantes.fr.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Jaillardon
authors.affiliation: Oniris, Université Nantes-Angers-Le Mans, Department of Human Health, Biomedical Research and Animal Models, AMaROC Unit and LDHvet laboratory, Nantes Atlantic College of Veterinary Medicine, Food Science and Engineering, Site de la Chantrerie, Route de Gachet, Nantes, F-44307, France. jerome.abadie@oniris-nantes.fr.
authors.forename: Jérome
authors.initials: J
authors.lastname: Abadie
authors.affiliation: Oniris, Université Nantes-Angers-Le Mans, Department of Human Health, Biomedical Research and Animal Models, AMaROC Unit and LDHvet laboratory, Nantes Atlantic College of Veterinary Medicine, Food Science and Engineering, Site de la Chantrerie, Route de Gachet, Nantes, F-44307, France. tiffanie18@hotmail.fr.
authors.forename: Tiffanie
authors.initials: T
authors.lastname: Godard
authors.affiliation: Institut de Cancérologie de l'Ouest, Boulevard Jacques Monod Saint Herblain-Nantes cedex, Centre de Recherche du Cancer Nantes-Angers, UMR-INSERM U892/CNRS 6299, Nantes, F-44805, France. mario.campone@ico.unicancer.fr.
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.affiliation: Hopital G&R Laënnec, Boulevard Jacques Monod, Saint Herblain-Nantes cedex, Nantes, F-44093, France. delphine.loussouarn@chu-nantes.fr.
authors.forename: Delphine
authors.initials: D
authors.lastname: Loussouarn
authors.affiliation: Oniris, Université Nantes-Angers-Le Mans, Department of Human Health, Biomedical Research and Animal Models, AMaROC Unit and LDHvet laboratory, Nantes Atlantic College of Veterinary Medicine, Food Science and Engineering, Site de la Chantrerie, Route de Gachet, Nantes, F-44307, France. brigitte.siliart@oniris-nantes.fr.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Siliart
authors.affiliation: Oniris, Université Nantes-Angers-Le Mans, Department of Human Health, Biomedical Research and Animal Models, AMaROC Unit and LDHvet laboratory, Nantes Atlantic College of Veterinary Medicine, Food Science and Engineering, Site de la Chantrerie, Route de Gachet, Nantes, F-44307, France. frederique.nguyen@oniris-nantes.fr.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Nguyen
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D015870:Gene Expression; D016130:Immunophenotyping; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D017526:Receptor, IGF Type 1