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

Jérôme Abadie,Ingrid Bemelmans,Anton Belousov,Adelina Gama,Laëtitia Jaillardon,Laura Peña,Delphine Loussouarn,Natascha Rieder,Frédérique Nguyen,Mario Campone,Catherine Ibisch

doi:10.1007/s10549-017-4542-8

Abstract

PurposeRelevant 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.MethodsThree 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.ResultsFour 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.ConclusionsIn 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.

Highlights

Human breast cancer is a complex disease encompassing different entities with considerable variation in clinical, phenotypical, and molecular attributes [1]
The basal-like subtype represents a subset of triple-negative breast cancers (TNBCs), which expresses genes ordinarily expressed in the basal/myoepithelial cell compartment of normal breast as well as epidermal growth factor receptor (EGFR)
This study aims to contribute to the evaluation of these tumors as potent preclinical models for human breast cancer

Summary

Introduction

Human breast cancer is a complex disease encompassing different entities with considerable variation in clinical, phenotypical, and molecular attributes [1]. Expression of estrogen receptor alpha (ERα), progesterone receptor (PR) and overexpression of the human epidermal growth factor receptor 2 (HER2) have been included to redefine classification, predict prognosis, and guide therapy in routine clinical practice [3,4,5,6]. The roles of these three biomarkers have been reinforced thanks to progress in molecular analysis and understanding of breast cancer biology [7,8,9,10]. The spectrum of triplenegative/basal-like breast cancers is wide but, clinically, most patients have a very poor prognosis with currently no targeted therapy [12]

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