The transition from a normal to a cancerous cell involves a multistep process driven by genetic alterations. Malignant cells progressively acquire traits that enhance their survival within the host, including the ability to evade apoptosis, stimulate neovascularization, and escape immune surveillance. These adaptations allow cancer to grow uncontrollably, invade adjacent tissues, and metastasize to distant organs, ultimately impairing normal physiological functions and complicating treatment efforts. Among the most significant clinical challenges is chemotherapy resistance, which diminishes the effectiveness of conventional therapies and contributes to disease progression. Addressing this issue requires integrated and multidisciplinary approaches. This review investigates and compares the mechanisms of chemotherapy resistance identified in humans and companion animals. By examining both shared and species-specific features, this analysis aims to support the development of more effective and translational treatment strategies.

The tumor microenvironment (TME) plays a central role in cancer progression, with tumor-associated macrophages (TAMs) and extracellular matrix (ECM) components such as collagen being key modulators of invasiveness and immune regulation. Although macrophage infiltration and ECM remodeling are well-documented individually, their coordinated contribution to mammary carcinoma aggressiveness remains underexplored, particularly in comparative oncology models. This study analyzed 117 mammary carcinoma samples—59 from dogs and 58 from women—using immunohistochemistry, immunofluorescence, and second-harmonic-generation (SHG) microscopy. We quantified TAM density and phenotype (CD206, iNOS, and S100A8/A9), assessed collagen fiber organization, and examined correlations with clinical–pathological variables and overall survival. Increased TAM infiltration was associated with a higher histological grade, aggressive molecular subtypes, enhanced cell proliferation, and shortened survival in dogs. High TAM density also correlated with decreased collagen fiber length and increased alignment, suggesting active immune–matrix remodeling in aggressive tumors. Macrophage phenotyping revealed heterogeneous populations, with CD206⁺ cells predominating in high-grade tumors, while S100A8/A9⁺/iNOS⁺ phenotypes were enriched in less aggressive subtypes. The findings were consistent across species, reinforcing the relevance of canine models. Our results identify macrophage–collagen interactions as critical determinants of tumor aggressiveness in mammary carcinomas. This study bridges comparative oncology and translational research by proposing immune–ECM signatures as potential prognostic biomarkers and therapeutic targets. These insights contribute to the advancement of molecular oncology in Brazil by supporting innovative strategies that integrate immune modulation and matrix-targeted interventions in breast cancer.

The malignant adenomyoepithelioma is a rare mammary tumor in women and uncommon in cats with only one report in this species. In this case report, the histopathological and immunohistochemical characteristics of six cases of malignant adenomyopithelioma in the feline mammary gland are described. Microscopic evaluation of tumors showed dense cellular neoplastic proliferation, composed of malignant myoepithelial and epithelial cells, formed by varied arrangements and presenting papillary, tubular and solid nest proliferation. Immunohistochemistry was performed for markers Ki67, Cox-2, RE, RP, p63 and HER-2. All cases were positive for p63, confirming the myoepithelial nature of neoplastic cells. The diagnosis of malignant adenomyopithelioma was made possible through the association between histopathological characteristics and immunohistochemical results.

New diagnostic and therapeutic approaches have been increasingly demanded due to the high morbidity and mortality associated with breast cancer. Recently, changes in the collagen fibres in mammary neoplasms have been shown to provide information that can be helpful for more accurate diagnosis. We aimed to conduct a comparative analysis of the tumour stroma in human and canine mammary neoplasms to assess the relationship between collagen modifications and the behaviour of carcinomas in both species, by multiphoton microscopy. We present a retrospective study of 70 cases of human mammary tumour and 74 cases of canine mammary tumour. We analysed sections stained with haematoxylin and eosin from 1,200 representative areas of normal mammary tissue, fibroadenoma, grade I invasive carcinoma, grade III invasive carcinoma and invasive micropapillary carcinoma in human species and 1,304 representative areas of normal mammary tissue, benign mixed tumour, mixed carcinoma, carcinosarcoma, invasive micropapillary carcinoma and solid carcinoma in canine species. We obtained that both human and canine mammary carcinomas present lower density of collagen fibres, higher density of cells and the collagen fibres are more aligned than in normal tissue. For human mammary carcinomas, the collagen fibres are more linear as compared to normal tissue. In addition, we demonstrated that the carcinomas with unfavourable prognosis present shorter collagen fibres, and these collagen changes correlate with the clinical and pathological data in human and canine species. For dogs, there is a correlation between the mean fibre length with the specific survival times. Thus, we demonstrate that dogs provide an excellent comparative perspective for studying how changes in the tumour stroma affect patient survival.