Canine mammary tumors as a model for human disease

Abstract

Animal models for examining human breast cancer (HBC) carcinogenesis have been extensively studied and proposed. With the recent advent of immunotherapy, significant attention has been focused on the dog as a model for human cancer. Dogs develop mammary tumors and other cancer types spontaneously with an intact immune system, which exhibit a number of clinical and molecular similarities to HBC. In addition to the spontaneous tumor presentation, the clinical similarities between human and canine mammary tumors (CMT) include the age at onset, hormonal etiology and course of the diseases. Furthermore, factors that affect the disease outcome, including tumor size, stage and lymph node invasion, are similar in HBC and CMT. Similarly, the molecular characteristics of steroid receptor, epidermal growth factor, proliferation marker, metalloproteinase and cyclooxygenase expression, and the mutation of the p53 tumor suppressor gene in CMT, mimic HBC. Furthermore, ductal carcinomas in situ in human and canine mammary glands are particularly similar in their pathological, molecular and visual characteristics. These CMT characteristics and their similarities to HBC indicate that the dog could be an excellent model for the study of human disease. These similarities are discussed in detail in the present review, and are compared with the in vitro and other in vivo animal models available.

Keywords: breast cancer; canine; cat; cell lines; dog; mammary tumors; mice; model; rat; rodent; xenografts.

Figure 1.

Mammary intraepithelial lesions in canine and human mammary biopsies. Hematoxylin and eosin-stained mammary biopsies of normal (upper part), and carcinoma gland (lower part). Magnification, ×200. Modified with permission from Antuofermo et al (93).