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

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.

Fig. 1

Algorithms of immunohistochemical classifications of canine mammary carcinomas adapted from Nielsen (A) and Blows (Β)

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