Abstract LB-46: Spontaneous canine mammary carcinomas as a model of human triple-negative 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 innovative therapies are needed. Recent studies indicate that spontaneous canine mammary carcinomas (CMCs) resemble human breast cancers, by histopathology, tumour genetics, and biological behaviour. 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 194 cases. The mean age at diagnosis was 10.8±2.1 years. 31% of dogs were neutered females. 14% were alive at the end of the study. The most common histologic subtype was simple tubulopapillary CMC (53%), then solid CMC (32%). The most common grades were grade II (47%) and III (41%). 47% of the tumours showed lymphatic emboli. 4 immunophenotypes were defined: luminal A (16=8%), luminal B (7=4%), basal-like (110=56%) and non basal-like (38=20%) triple negative CMCs. 23 (12%) 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: the dog weight at diagnosis (p=0.015), histologic subtype (p=0.0006), histologic grade (p=0.003), presence of emboli (p=0.0001) or lymph node metastasis (p=0.005), ER positivity (p=0.046), and the Ki67 index (p=0.01). Triple-negative carcinomas showed a shorter specific survival (median=210 days) when compared to luminal A CMCs (672 days) (p=0.04). Conclusion: Preliminary data based on 194 animals indicate that the molecular classification of human breast cancer identifies in dogs 4 subtypes with different prognoses. 76% of CMCs were of the triple-negative subtype, and associated with shorter specific survival, as reported in human breast cancer. Final data based on 350 animals will be presented at the meeting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-46. doi:10.1158/1538-7445.AM2011-LB-46