Comparative oncology research in Australia: establishing the Australian Veterinary Cancer Biobank to validate canine mammary tumours as a model for human breast cancer

There is a strong degree of conservation and similarity in the pathobiology of mammary tumours in humans and dogs. These tumours share many similar biological and clinical features. To help provide a long-term comparative oncology resource this study established Australia’s first canine mammary tumour biobank; the Australian Veterinary Cancer Biobank (AVCBB). This biobank created a novel structure that utilized remote biobanking from a network of 56 veterinary clinics and three veterinary pathology services across Victoria, Australia. For this research a novel sample collection kit, the Dog Mammary Tissue Collection (DogMATIC) kit was developed, to support the remote collection of canine mammary tumour samples.<br><br>This research is the first to investigate survival of different breeds in Australia with mammary tumours. In addition, contemporary international studies lack representation of popular Australian breeds such as Jack Russell Terriers, Australian Cattle Dogs and Kelpies. Using the samples and follow-up data collected by the AVCBB this research demonstrated that nearly 40% of Canine Mammary Tumours (CMTs) in Australian dogs are malignant and occur in intact bitches. Additionally, Jack Russell Terriers, Kelpies, Pomeranians and Shih Tzus may be at higher risk of developing CMTs; whilst Gun dogs were more likely to develop a benign tumour. CMTs were more common in older dogs with peak onset at 10.5 years. Recurrence occured in nearly 10% of dogs with a malignant tumour. Malignant mammary tumours significantly impacted animal survival with most likely to die from their tumour or its metastasis. This study also investigated the distribution and survival of breast cancer subtypes, used to classify breast cancers in humans, in Australian dogs. The results showed that basal-like tumours were the most common and were more likely to be found in pure bred dogs. Most importantly, this subtype was significantly associated with death.<br><br>As veterinary pathologists are more frequently asked to provide an opinion on the prognosis of cases this research also evaluated the potential of three new prognostic markers; parathyroid hormone-related protein (PTHrP), runt related transcription factor 2 (Runx2) and GATA binding protein 3 (GATA-3). The first of which, PTHrP, belongs to a gene family that has been implicated in both breast cancer and osteosarcoma. This study investigated the role of PTHrP in both CMTs and a mouse model of osteosarcoma. In CMTs, PTHrP did not provide any prognostic value. Whereas, in the osteosarcoma model the loss of the receptor for PTHrP, PTHR1, produced a more differentiated tumour phenotype with increased mineralized osteoid and significantly diminished proliferation. Of the three markers tested Runx2 had the most potential as a prognostic marker. Runx2 over-expressing tumours were associated with an aggressive phenotype and poorer survival. Animals with Runx2 over-expressing tumours were at higher risk of tumour progression and a poor outcome.<br><br>Together the findings of this research support the development of biobanking for comparative oncology research in Australia and the use of canine mammary tumours as a model for human breast cancer. Finally, that both the molecular subtypes of human breast cancer and the over-expression of Runx2 can be used in veterinary pathology to provide information on the prognosis of animals with malignant canine mammary tumours