Genomic instability in canine mammary tumors: A comparative focus on loss of heterozygosity and microsatellite alterations with human breast cancer.

Canine mammary tumors (CMTs) are the most prevalent neoplasms in intact female dogs, accounting for up to 50% of all neoplasms, with malignancy rates ranging from 50% to 89%. Human breast cancer (HBC) remains a leading cause of cancer morbidity and mortality worldwide. Both diseases exhibit remarkable biological and molecular similarity, making the domestic dog an excellent spontaneous model for studying HBC. CMTs and HBC share histopathological features. They also have comparable classification systems, including hormone receptor-based subtypes (luminal A, luminal B, HER2-positive) and the triple-negative subtype, as well as dysregulation of pathways such as PI3K/AKT and Wnt/β-catenin. Furthermore, they share several risk factors and environmental determinants. In contrast to rodent models, dogs offer natural genetic variation and comparable environmental exposures, enabling more physiological studies of cancer development. This review focuses on genomic instability, specifically microsatellite instability (MSI) and loss of heterozygosity (LOH), as an important driver of neoplastic growth in both species. MSI results from DNA mismatch repair defects, whereas LOH indicates tumor suppressor gene inactivation. Emerging evidence shows that these alterations occur in CMTs just as they do in HBC. Investigating MSI and LOH in dogs can uncover common molecular mechanisms, identify reliable biomarkers, and reveal novel therapeutic targets. Ultimately, this comparative approach reinforces the "One Health" concept, bridging veterinary and human medicine to improve cancer outcomes for both species.