This study describes the clinical and histopathological findings in dogs with mammary gland tumours, and compares the histopathological and clinical evidence consistent with progression from benign to malignant to human breast cancer epidemiology. Clinical and histopathological data on 90 female dogs with 236 tumours was included. Dogs with malignant tumours were significantly older than dogs with benign tumours (9.5 versus 8.5 years), P = 0.009. Malignant tumours were significantly larger than benign tumours (4.7 versus 2.1 cm), P = 0.0002. Sixty-six percent had more than one tumour, and evidence of histological progression was noted with increasing tumour size. Dogs with malignant tumours were significantly more likely to develop new primary tumours than dogs with benign tumours, P = 0.015. These findings suggest that canine mammary tumours progress from benign to malignant; malignant tumours may be the end stage of a histological continuum with clinical and histopathological similarities to human breast carcinogenesis.
Increasing evidence indicates that the tumor microenvironment plays a critical role in regulating the biologic behavior of breast cancer. In veterinary oncology, there is a need for improved prognostic markers to accurately identify dogs at risk for local and distant (metastatic) recurrence of mammary gland carcinoma and therefore would benefit from adjuvant therapy. Collagen density and fiber organization have been shown to regulate tumor progression in both mouse and human mammary tumors, with certain collagen signatures predicting poor outcomes in women with breast cancer. We hypothesized that collagen signatures in canine mammary tumor biopsies can serve as prognostic biomarkers and potential targets for treatment. We used second harmonic generation imaging to evaluate fibrillar collagen density, the presence of a tumor-stromal boundary, tumor associated collagen signatures (TACS) and individual collagen fiber characteristics (width, length and straightness) in grade I/II and grade III canine mammary tumors. Collagen density, as well as fiber width, length and straightness, were inversely correlated with patient overall survival time. Notably, grade III cases were less likely to have a tumor-stromal boundary and the lack of a boundary predicted poor outcome. Importantly, a lack of a defined tumor-stromal boundary and an increased collagen fiber width were associated with decreased survival even when tumor grade, patient stage, ovariohysterectomy status at the time of mammary tumor excision, and histologic evidence of lymphovascular invasion were considered in a multivariable model, indicating that these parameters could augment current methods to identify patients at high risk for local or metastatic progression/recurrence. Furthermore, these data, which identify for the first time, prognostic collagen biomarkers in naturally occurring mammary gland neoplasia in the dog, support the use of the dog as a translational model for tumor-stromal interactions in breast cancer.
BackgroundOvarian hormones play crucial roles in mammary carcinogenesis. However, whether ovarian ablation by ovariohysterectomy (OHE) improves the prognosis in dogs with mammary carcinomas is unclear.ObjectivesDetermine if OHE at the time of mastectomy improves the prognosis in dogs with mammary carcinomas and evaluate if hormonal factors influence the effect of OHE.AnimalsSixty intact dogs with mammary carcinomas.MethodsDogs were randomly assigned in a 1 : 1 ratio to undergo OHE (n = 31) or not (n = 29) at the time of tumor removal. Peri‐surgical serum estradiol (E2) and progesterone concentrations were measured, tumor diagnosis was confirmed histologically, and tumor estrogen and progesterone receptor status was immunohistochemically determined. The dogs were monitored for recurrence and metastases every 3‐4 months for at least 2 years. Uni‐ and multivariable survival analyses were performed with relapse and all‐cause death as endpoints in addition to univariable subgroup analyses.ResultsOverall, OHE did not significantly decrease hazard of relapse (hazard ratio [HR], 0.64; P = .18) or all‐cause death (HR, 0.87; P = .64) in univariable analyses. In multivariable analysis OHE did not significantly influence the hazard of relapse (HR, 0.54; P = .12), but an interaction effect was identified between ER status and E2 (P = .037). Subgroup analysis identified decreased hazard of relapse in the OHE group compared to the non‐OHE group in the subsets of dogs with increased E2 (HR, 0.22; P = .012) or grade 2 tumors (HR, 0.26; P = .02).ConclusionDogs with grade 2, ER‐positive tumors, or with increased peri‐surgical serum E2 concentration represent a subset of dogs with mammary carcinomas likely to benefit from OHE.
Background: Age-related changes in renal histomorphology are described, while the presence of glomerulonephritis in dogs with pyometra is controversial in current literature.
Background: Nonmalignant mammary tumors (NMT) are common in intact female dogs. Little is known about the clinical significance of these tumors, and the effect of ovariohysterectomy (OHE) on their development.Hypothesis: Ovarian hormone ablation through OHE decreases the risk of new tumors and thereby improves long-term prognosis for dogs with NMT.Animals: Eighty-four sexually intact bitches with NMT. Methods: Dogs were allocated to undergo OHE (n = 42) or not (n = 42) at the time of NMT removal in a randomized clinical trial. Tumor diagnosis was confirmed histologically in all subjects. Information about new tumor development was collected via follow-up phone calls and recheck examinations. Separate survival analyses were performed with the endpoints new tumor development and death. Cause of death was classified as related or unrelated to mammary tumor. In addition to OHE status, the influence of age, body weight, breed, tumor size, tumor number, tumor duration, type of surgery, and tumor histology was investigated.Results: New mammary tumor(s) developed in 27 of 42 (64%) intact dogs and 15 of 42 (36%) ovariohysterectomized dogs (hazard ratio 0.47, P = .022). Nine of the 42 dogs (21%) which developed new tumors were euthanized because of mammary tumor. Survival was not significantly different between the 2 treatment groups. In the intact group, nine dogs subsequently developed ovarian-uterine diseases.Conclusion: Ovariohysterectomy performed at the time of mammary tumor excision reduced the risk of new tumors by about 50% among dogs with NMT. Survival was not significantly affected. Adjuvant OHE should be considered in adult dogs with mammary tumors.
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