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  • Feline Mammary Carcinoma – Challenges and Advances in Veterinary Oncology

  • Erfan Eftekhar ,1 Noushin Farandpour,2 Shahin Darvishi,3 Ronak Aziz beigi,4,* Ali Karamian,5
    1. Student in Veterinary Medicine, Sanandaj Branch, Islamic Azad University, Sanandaj , Iran
    2. Student in Veterinary Medicine, Sanandaj Branch, Islamic Azad University, Sanandaj , Iran
    3. Doctoral student in General Veterinary Medicine, Razi University of Medical Sciences, Kermanshah, Iran
    4. Department of Basic Sciences, Sa.C., Islamic Azad University, Sanandaj, Iran
    5. Assistant Professor, Faculty of Veterinary Medicine, Razi University


  • Introduction: Feline mammary carcinoma (FMC) is one of the most common neoplasms in older female cats and poses a significant challenge in veterinary oncology due to its aggressive behavior. Approximately 85–90% of feline mammary tumors are malignant, typically presenting as invasive carcinomas with a high propensity for metastasis to regional lymph nodes, lungs, and other organs. The etiology is multifactorial; however, sex hormones play a crucial role, with prolonged exposure to estrogen and progesterone implicated in tumor development. Early ovariohysterectomy—ideally before 6 months or up to 1 year of age—has been shown to reduce the risk significantly (by up to 91%). Additional risk factors include advanced age (mean 10–12 years) and breed predispositions (e.g., Siamese cats), making FMC both a critical clinical problem and a valuable model for comparative oncology with human breast cancer.
  • Methods: This article is a comprehensive review based on the collection and critical evaluation of existing research on FMC. The literature covers various interconnected aspects: epidemiology and risk factors (including age, hormonal status, breed, and neutering timing), molecular pathogenesis (focusing on signaling pathways and genetic markers such as HER2/neu, EGFR, VEGF, VISTA, leptin/ObR, miR-10b, and genetic variants in BRCA1/2), as well as clinical presentation and staging. Definitive diagnosis is established via histopathology and imaging modalities (CT and ultrasound), while the TNM system is employed for staging. Conventional treatment approaches—such as radical mastectomy (unilateral or bilateral) combined with adjuvant chemotherapy (commonly doxorubicin-based)—are evaluated alongside emerging therapeutic strategies, including tyrosine kinase inhibitors, immunotherapy targeting immune checkpoints (PD-1/PD-L1, CTLA-4, VISTA), and experimental anti-miR-10b treatments.
  • Results: FMC is characterized by an overwhelmingly high malignancy rate and an aggressive clinical course. Epidemiological studies report incidence rates in specific regions (e.g., 438 cases per 100,000 cats in certain Russian populations) and reveal a malignant to benign tumor ratio of approximately 9:1 in North America. Molecular analyses indicate that overexpression of HER2/neu is common in 76.7–90% of cases, and emerging biomarkers—such as VISTA (which shows elevated serum levels in HER2-positive and triple-negative FMC subtypes), altered levels of leptin and its receptor, and upregulated miR-10b in metastatic lesions—are garnering interest for both diagnostic and therapeutic purposes. Genetic investigations have also identified mutations in BRCA1/2 in a subset of FMC cases, suggesting a hereditary component. Notably, a “luminal-AR” subtype (characterized by AR+ FOXA1+ CK14– expression) within triple-negative FMC has been correlated with a better prognosis. While radical mastectomy remains the cornerstone of management, adjuvant chemotherapy is widely used to address micrometastatic disease; however, its definitive long-term benefit continues to be debated. Novel approaches, including molecularly targeted therapies and immunotherapeutic regimes, are under active investigation and show promise.
  • Conclusion: Feline mammary carcinoma remains a formidable challenge due to its high rate of malignancy, rapid progression, and limited effective treatment options. Preventive strategies, particularly early neutering, and early diagnosis via aggressive surgical intervention are essential for optimal management. Advances in understanding the molecular and genetic underpinnings of FMC have paved the way for the development of targeted therapies and improved prognostic indicators. Moreover, given the striking pathological and molecular similarities between FMC and aggressive subtypes of human breast cancer (such as HER2-positive and triple-negative forms), the cat stands as a valuable natural model for comparative oncology research. Future directions should focus on the clinical validation of novel biomarkers, refinement of combination therapeutic strategies to overcome treatment resistance, and the reduction of metastasis, ultimately aiming to enhance clinical outcomes for both veterinary patients and, by translational extension, human breast cancer research.
  • Keywords: Bioinformatics, Feline Mammary Carcinoma, Molecular Biomarkers, Comparative Oncology, Targeted Thera

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