PD08-10: High Frequency of Triple Negative Mammary Carcinomas in the Dog as Model of Human Breast Cancer.

Abstract

Abstract Background Information: Relevant animal models of human breast cancer are currently lacking, especially regarding the triple-negative breast cancer (TNBC) subtype, for which efficient therapies are needed. Recent studies indicate that spontaneous canine mammary carcinomas (CMCs) (which are common in France due to absence of early neutering) resemble human breast cancers, by pathology, tumor genetics, and biological behavior. However, the current molecular classification of human breast cancer has not been evaluated in canine samples yet. Objective: To establish the prognostic value of the human immunophenotypic classification in dogs To evaluate CMCs as a model of human breast cancer including TNBC. Methods: 350 CMCs treated by surgery alone were obtained from the Nantes Atlantic College of Veterinary Medicine, Food Science and Engineering (France) from 2005 to 2008. Recorded clinical data included breed, neutering, age at diagnosis, presence of metastases, cause and time to death. Histological records included the subtype of carcinoma, Elston & Ellis grade, presence of emboli and lymph node metastasis. By immunohistochemistry (IHC) using ER, PR, Her2 (Herceptest and Pathway® Her2), CK5/6, EGF-R and KI67, CMCs were classified into the subtypes of human breast cancer according to Nielsen et al. IHC analyses were independently reviewed by four pathologists. Results: The preliminary data in this abstract are based on 200 cases. The mean age at diagnosis was 10.8±2.1 years. 72,7% of dogs were intact female (27,3% of late neutering). 41% of dogs died due to cancer progression (metastasis rate of 30%). The most common histologic subtype was simple tubulopapillary CMC (53%), then solid CMC (32%). The most common grades were grade II (49%) and III (43%). 53% of the tumours showed lymphatic emboli. 4 immunophenotypes were defined: luminal A (11.9%), luminal B (5.1%), basal-like (59.3%) and non basal-like (23.7%) triple negative CMCs. 8.8% of the CMCs were scored Her2 2+ but none were considered Her2-overexpressing as defined by a 3+ score, despite appropriate staining with the two well established methods. Predictive factors for specific survival were: dog weight (p=0.01), histologic subtype (p=0.001), presence of emboli (p<0.0001) or lymph node metastasis (p=0.02), Ki67 index (p=0.03). Triple-negative carcinomas showed a significantly shorter specific survival (median=224 days) when compared to luminal A CMCs (median=641 days) (MannWhitney, p=0.016). Conclusion: The molecular classification of human breast cancer identifies 4 subtypes of invasive CMCs with different prognoses. In dogs, a low rate of luminal tumors are observed, and no Her2-overexpressing tumors are found (defined by a score of 3+ by Her2 immunohistochemistry). 83% of CMCs were of the triple-negative subtype, associated with a shorter survival, as reported in human breast cancer. Infiltrative mammary cancer in dogs could be an interesting model for preclinical investigations. Final data based on 350 animals will be presented at the meeting. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD08-10.