Canine mammary tumours, an overview

Canine mammary tumours (CMTs) are the most common neoplasms in intact female dogs. Although the prevalence of these tumours decreases in regions where preventive ovari(ohyster)ectomy is performed, it remains an important disease entity in veterinary medicine. Moreover, treatment options are limited in comparison with human breast cancer. Nevertheless, recent human treatment protocols might have potential in bitches suffering from CMTs.     

Canine mammary mixed tumours: immunohistochemical expressions of EGFR and HER‐2

Background Benign mixed tumours (BMTs) are frequently found in the mammary glands of female dogs, but the factors determining malignant transformation in these tumours are unknown. Objective To evaluate the expression of the oncoproteins, human epidermal growth factor receptor 2 (HER‐2) and epidermal growth factor receptor (EGFR), in 46 carcinomas in BMTs (CBMTs) and to verify their possible association with the malignancy of the tumours. Methods Immunohistochemical expression was analysed in benign and malignant components separately, and then compared with 74 cases of BMTs. Results Among the CBMTs, positivity for HER‐2 was found in the benign histological component of 4.3% (2/46), in the malignant epithelial non‐invasive component of 14.8% (4/27) and in the malignant invasive epithelial component of 13.6% (6/44) of cases. Two of the 24 (8.3%) BMTs were positive for HER‐2. There was no relationship between HER‐2 and the tumour components. There was no significant difference between BMTs and CBMTs. Positivity for EGFR was found in the benign component of 17.4% (8/46) of the CBMTs, in the malignant epithelial non‐invasive component of 40.7% (11/27%) and in the invasive epithelial malignant component of 45.4% (20/44). EGFR positivity was significantly associated with the invasive component of CBMTs. Conclusion EGFR may contribute to malignant epithelial transformation of BMTs. In contrast, HER‐2 overexpression may not be associated with the acquisition of a malignant epithelial phenotype.     

Influence of ovariectomy at the time of mastectomy on the prognosis for canine malignant mammary tumours

The two-year prognosis for malignant mammary tumours seen in 175 bitches in the Tokyo metropolitan area was assessed based on the extent of mastectomy and on whether an ovariectomy was carried out at the time of mastectomy. The prognosis for the bitches was not influenced by the excision size of the affected mammary glands. Ovariectomy had no effect on the two-year survival rate of the dogs that underwent the tumour excision. There was no significant difference in the two-year survival rate between the dogs ovariectomised prior to mastectomy and those ovariectomised at the time of mastectomy. These results suggest that ovariectomy at the time of mastectomy has no effect on the prognosis in dogs with established neoplasms of the mammary gland.     

Canine haemangiopericytomas--a survey of 200 tumours

Abstract— —Of 200 canine haemangiopericytomas examined, most were slow-growing, lobulated tumours which occurred principally in dogs between 6 and 14 years of age. Haemangiopericytomas were found more often in females (69 per cent) and in two sites, the forelegs (26 per cent) and thighs (26 per cent). The next most common locations were the chest (11 per cent) and shoulders (8 per cent). Compared to the normal canine population, the haemangiopericytoma is more prevalent in Boxer dogs, German Shepherd dogs, Cocker and Springer Spaniels. Résumé— —Parmi 200 hemangiopéricytomes examinés chez le chien, la plupart sont des tumeurs lobuées à croissance lente, qui apparaissent chez des animaux âgés de 6 à 14 ans. Les hémangio-péricytomes sont rencontrés plussouvent chez les femelles (69 p. 100) et selondeux localisations: sur les pattes postérieures (26 p. 100) et sur les cuisses (26 p. 100). Ensuite, les leiux d'élection les plus communs sont la poitrine (11 p. 100) et les épaules (8 p. 100). Compte-tenu de la répartition des races dans la population canine, l'hémangiopericytome est plus fréquent chez les boxers, les bergers allemands. les cockers et les épagneuls. Zusammenfassung— —200 Hämangioperizytome von Hunden wurden untersucht. Die mcisten erwiesen sich als lobuläre Tumoren von langsamer Wachtumsgeschwindigkeit, die hauptäschlich bei Hunden im Alter zwischen 6 und 14 Jahren gefunden wurden. Hämangioperizytome wurden mit größerer Häufigkeit bei Hündinncn (69 Prozent) und in 2 Körperteilen, dem Vorderbein (26 Prozent) und dem Oberschenkel (26 Prozent), gesehen. Die beiden nächsthäufigen Vorkommensorte waren die Brust (11 Prozent) und die Schultern (8 Prozent). Im Verhältnis zur normalen Hundebe-völkerung erscheint sin Hämangioperizytom mit größerer Frequenz bei Boxern, Deutschen Schäfer-hunden, Cocker- und Springerspanieln.     

Canine mammary gland tumours; a histological continuum from benign to malignant; clinical and histopathological evidence*

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.     

The effect of neutering on the risk of mammary tumours in dogs--a systematic review

A commonly-stated advantage of neutering bitches is a significant reduction in the risk of mammary tumours, however the evidence for this has not previously been assessed by systematic review. The objectives of this study were to estimate the magnitude and strength of evidence for any effect of neutering, or age of neutering, on the risk of mammary tumours in bitches. A systematic review was conducted based on Cochrane guidelines. Peer-reviewed analytic journal articles in English were eligible and were assessed for risk of bias by two reviewers independently. Of 11,149 search results, 13 reports in English-language peer-reviewed journals addressed the association between neutering/age at neutering and mammary tumours. Nine were judged to have a high risk of bias. The remaining four were classified as having a moderate risk of bias. One study found an association between neutering and a reduced risk of mammary tumours. Two studies found no evidence of an association. One reported "some protective effect" of neutering on the risk of mammary tumours, but no numbers were presented. Due to the limited evidence available and the risk of bias in the published results, the evidence that neutering reduces the risk of mammary neoplasia, and the evidence that age at neutering has an effect, are judged to be weak and are not a sound basis for firm recommendations.     

Activation of AKT in feline mammary carcinoma: a new prognostic factor for feline mammary tumours

The PI3K/AKT/PTEN pathway is involved in the pathogenesis of several human cancers. This study investigated the biological and prognostic value of PI3K/AKT/PTEN pathway dysregulation in feline mammary tumours. Expression of p-AKT, HER2, PTEN and steroid receptors was assessed by immunohistochemistry (IHC) in 27 malignant and 12 benign mammary tumours from 39 female cats followed up over a 24-month period. Feline mammary carcinoma (FMC) cell lines were analyzed by Western blot and the feline AKT gene sequence was characterized. p-AKT expression statistically correlated with tumour malignancy, histological dedifferentiation and clinical recurrence. The animals with tumours expressing p-AKT had a shorter disease-free period than those with p-AKT-negative tumours. AKT activation was associated with HER2 expression and PTEN down-regulation, as occurs in human breast cancer, and feline AKT sequencing showed high homology with the human AKT gene. No AKT activation was observed in relation to either oestrogen receptor α (ERα) or progesterone receptor expression. Taken together, these data offer an explanation for AKT signalling and its role in FMC pathogenesis and prognosis, shedding new light on similarities between feline mammary tumours and hormone-independent breast cancer.     

Microtomographic characterization of calcifications in canine mammary tumours

The present work describes the microtomographic characterization of macro‐ and microcalcifications present in excised canine mammary glands. In human breast cancer, microcalcifications are highly relevant for diagnosis and prognosis, often being the sole element determining biopsy. Canine mammary tumours are considered a model for human breast cancer, but the morphological features of calcifications had still to be studied in this species. The objective of this research is to contribute to the characterization of the mineralization features of the canine mammary gland. In the present study, the excised mammary glands of 33 bitches underwent fluoroscopic examination. In 30 of the samples, the presence of calcification was suspected, and multiple biopsies were taken of these areas. Biopsy fragments underwent microtomographic scanning. Microcalcifications were found in non‐neoplastic glandular tissue, benign and malign lesions, as it is known to happen in humans. Qualitative evaluation regarding morphology of the imaged calcifications showed similarities to breast cancer findings, based on the BI‐RADS 2013 classification, such as pleomorphism and shape. No differences in the quantitative morphological parameters of volume, surface, surface/volume, SMI and structure thickness were found when macrocalcifications were considered. However, although significant differences existed in these parameters between microcalcifications from malignant canine mammary tumours and the two other groups, none were found between non‐neoplastic and benign tumours. Findings further support the use of this spontaneous animal model for the study of human breast cancer, considering how clinically relevant microcalcifications are in humans.     

Distribution of nuclear DNA-content in canine mammary tumours

It is well established that nuclear DNA-content contributes valuable information concerning tumour behaviour in a vast number of human neoplasms (compare Auer and Zetterberg, 1984 and Zetterberg and Auer 1984 for review). The authors have attempted for the first time to apply this concept to clinical veterinary medicine and in the present investigation 17 dogs with mammary tumour were studied retrospectively. Microspectro-photometric DNA-measurements were performed and correlated to the clinical course defined as distant recurrence free interval. The results suggest that a relationship exists between nuclear DNA-content of the breast cancer cells and prognosis. Tumours exhibiting DNA-values within the limits of normal tissue correlate with a favourable prognosis in the sense that all dogs with diploid tumour cell DNA-content under study had survived for more than one year without recurrence of the tumour. In contrast 50 per cent of the tumours with increased and scattered DNA-values developed metastasis within one year whereas the other 50 per cent were disease free after this period. It is therefore proposed that cytophotometric analysis of DNA may be used in the assessment of prognosis in dogs with malignant breast tumours.     

Expression and significance of PTEN in canine mammary gland tumours

To explore the expression and clinical importance of the anti-oncogene phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in canine mammary gland tumours, PTEN expression was compared in 50 cases of canine mammary tumour and four examples of normal mammary tissue using real-time quantitative PCR. PTEN expression was similar in benign mammary tumours and normal mammary tissues (P>0.05), but was lower in malignant tumours than in normal mammary tissues or benign mammary tumours (P<0.001). PTEN expression was also low in the lymph node metastases of malignant mammary tumours. The expression profile of PTEN in malignant mammary tumours compared to those without lymph node metastasis varied significantly. Low-level PETN expression might play an important role in carcinogenesis and the progression of canine mammary tumours, and PTEN protein detection might be useful in evaluating tumour development and prognosis.     

Factors influencing the incidence and prognosis of canine mammary tumours

Factors relating to the incidence of canine mammary tumours are reviewed. Increased age, intact status or ovariectomy after 2.5 years of age, as well as progestagen treatment, can all lead to an increased risk of mammary neoplasia in the bitch. In addition, obesity early in life, and a habitual diet based on home-made food (rich in beef and pork, and poor in chicken) as opposed to commercial food, are also associated with the occurrence of mammary tumours. Other aspects related to incidence are also discussed. Increased age at diagnosis, invasive growth (fixed to adjacent tissues), large tumour size, ulceration of skin, and axillary or inguinal node involvement are clinical parameters associated with a low chance of survival after surgical excision of mammary tumours. Histological typing and grading of the tumour allows the establishment of a prognosis, which is poor where there is tumour proliferation as measured by S-phase fraction determination and Ki-67 immunostaining.