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. 2018 Jan;167(2):459-468.
doi: 10.1007/s10549-017-4542-8. Epub 2017 Oct 23.

Canine invasive mammary carcinomas as models of human breast cancer. Part 2: immunophenotypes and prognostic significance

Jérôme Abadie  1   2 , Frédérique Nguyen  3   4 , Delphine Loussouarn  4   5 , Laura Peña  6 , Adelina Gama  7 , Natascha Rieder  8 , Anton Belousov  9 , Ingrid Bemelmans  10 , Laëtitia Jaillardon  11 , Catherine Ibisch  3   4 , Mario Campone  4   12
Affiliations

Canine invasive mammary carcinomas as models of human breast cancer. Part 2: immunophenotypes and prognostic significance

Jérôme Abadie et al. Breast Cancer Res Treat. 2018 Jan.

Abstract

Purpose: Relevant animal models of human breast cancer are currently needed, especially for the aggressive triple-negative breast cancer subtype. Recent studies and our results (Part 1) indicate that spontaneous canine invasive mammary carcinomas (CMCs) resemble human breast cancer by clinics and pathology as well as behavior and prognostic indicators. We hypothesized that the current molecular classifications of human breast cancer, used for therapeutic decision, could be relevant to dogs.

Methods: Three hundred and fifty female dogs with spontaneous CMC and a 2-year follow-up were retrospectively included. By immunohistochemistry, CMCs were classified according to Nielsen (Clin Cancer Res 10:5367-5374, 2004) and Blows (PlosOne doi: 10.1371/journal.pmed.1000279, 2010) into the subtypes of human breast cancer.

Results: Four immunophenotypes were defined either according to Nielsen classification (luminal A 14.3%, luminal B 9.4%, triple-negative basal-like 58.6%, and triple-negative nonbasal-like 17.7% CMCs); or to Blows classification (luminal 1-: 11.4%, luminal 1+: 12.3%, Core basal phenotype: 58.6%, and five-negative phenotype: 17.7%). No HER2-overexpressing CMC as defined by a 3 + immunohistochemical score was observed in our cohort. By univariate and multivariate analyses, both immunophenotypical classifications applied to CMCs showed strong prognostic significance: luminal A or luminal 1+ CMCs showed a significantly longer disease-free interval (HR = 0.46), Overall (HR = 0.47), and Specific Survival (HR = 0.56) compared to triple-negative carcinomas, after adjustment for stage.

Conclusions: In our cohort, triple-negative CMCs largely predominated (76%), were much more prevalent than in human beings, and showed an aggressive natural behavior after mastectomy. Dogs are thus potent valuable spontaneous models to test new therapeutic strategies for this particular subtype of breast cancer.

Keywords: Animal model; Breast cancer; Dog; Immunophenotype; Luminal; Triple-negative.

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Conflict of interest statement

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The owners’ written consent and approval from the Oniris College of Veterinary Medicine local Animal Welfare Committee were obtained prior to inclusion of each canine mammary carcinoma in this retrospective observational study.

Figures

Fig. 1
Fig. 1
Algorithms of immunohistochemical classifications of canine mammary carcinomas adapted from Nielsen (A) and Blows (Β)
Fig. 2
Fig. 2
Cancer-specific survival in dogs with mammary carcinoma according to Nielsen (A) and Blows (B) classifications. A According to Nielsen et al. [8], luminal A tumors displayed significantly longer SS (HR = 0.39 [0.23–0.67], Logrank test p = 0.0006, Kaplan–Meier curves) than the other immunophenotypes. B According to Blows et al. [9], luminal 1+ tumors displayed significantly longer SS (HR = 0.43 [0.25–0.74], Logrank test p = 0.0023, Kaplan–Meier curves) than the other immunophenotypes
See this image and copyright information in PMC

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