1. Dealing with cancer in dogs: What this means to you and your Westie John Robertson VMD PhD Center for Comparative Oncology, Virginia Tech

2. Warning! This presentation contains a few pictures of cats and other critters

3. What’s this talk about? Tumors, neoplasms, cancer – what’s the difference? How common is cancer in dogs? How is cancer detected? What causes cancer? What do I do if my dog has a neoplasm? Transitional cell carcinoma in Scottish breed terriers Can the cancer epidemic in dogs be stopped?

4. Tumors, neoplasms, cancer Tumor – literally a swelling, but common term for a neoplasm Neoplasm – ‘new cells’; a mass of tissue derived from normal tissue that grows without normal regulation of growth Cancer – ‘The Crab’; a malignant neoplasm that grows by infiltration and which may spread to distant sites

5. Multicentric melanoma – Arabian Horse

7. How is cancer detected? The owner is the first person to know if a neoplasm is developing! – Changes in normal routine (loss of appetite, for example) (convulsions) – Detection of a growth (skin tumors are very common) – Persistent illness accompanied by discharges (vomiting, diarrhea, blood in urine are examples) – Weight gain, weight loss (in a relatively short time)

9. How is cancer detected? The veterinarian – Takes a careful history and does a thorough examination – Recommends further tests (blood work, radiographs, ultrasonography, surgical biopsy) – Communicates results to the owner – And as a team (owner, patient, veterinarian) make a decision on what to do!

11. Companion animals in the US There are many companion animals in the US – Dogs – 60 million + – Cats – 90 million + – Horses – 10 million+ – “Pocket pets” (hamsters, rats, mice, gerbils)

12. How common is cancer in dogs? Neoplastic disease is a (the) leading cause of death in dogs – 45% of dogs reaching middle age (about 6-7 years) will either develop a tumor, suffer medical complications as the result of a tumor, or die as the result of neoplastic disease (Source: Small Animal Clinical Oncology, Withrow and MacEwen, 3 rd ed., 2005)

13. What causes neoplasms (1)? All neoplasms, whether benign or malignant (cancer) are caused by mutation of critical genes that control cell growth, maturation and organization Mutation is irreversible, cell-to-cell inherited gene dysfunction Exposure to certain viruses, excessive radiation, and some chemicals can cause mutation

15. What causes neoplasms (2)? There are many inherited factors which increase the risk of developing neoplasms – Mutated, inherited genes – Genes linked to phenotype – Patterns of metabolism – Sensitivity to environmental exposures – Male/female gender – Increasing age – Concurrent diseases (immunosuppression)

17. Breed predispositions in purebred dogs to cancer Brachycephalic breeds (Boston Terriers, Boxers, Bulldogs, Mastiffs) – primary brain tumors Golden Retrievers – malignant lymphoma, hemangiosarcoma German Shepherds – hemangiosarcoma Giant breeds – appendicular osteosarcoma Scottish breed terriers – transitional cell carcinoma of urinary bladder

20. Therapies for malignancies in dogs Surgery is the primary modality for therapy of all canine tumors Chemotherapy is used to treat canine malignant lymphoma (about 25% of cases receive multiagent therapy) Radiation therapy is effective for some tumors Combination therapy is common

21. Review of VMRCVM oncology medical records 2004-2006

22. Results – Canine database 718 dogs in database search Top breeds in terms of incidence – Mixed breed (198)(26% of total cases) – Labrador Retriever (78)(11%) – Golden Retriever (46)(6%) – Cocker Spaniel (24)(3%) – Boxer (22)(3%) – ‘Other’(350)(49%)

23. Results – Age at presentation Canine (718 cases) – 0-3 yrs (46)(6%) – 4-6 yrs (75)(10%) – 7-10 yrs (345)(48%) – 11-14 yrs (224)(32%) – 15 yrs + (20)(3%) – Unknown (8)(1%) Feline (157 cases) – 0-3 yrs (12)(8%) – 4-6 yrs (20)(13%) – 7-10 yrs (36)(23%) – 11-14 yrs (66)(42%) – 15 yrs + (15)(10%) – Unknown (8)(5%)

24. Results – Category of diagnosis Canine (718 cases) – Benign (313 cases) – Malignant (343 cases) – Metastatic (62 cases) Feline (157 cases) – Benign (57 cases) – Malignant (73 cases) – Metastatic (27 cases)

25. Results - Outcomes Canine (718 cases) – Surgery (532)(74%) – Surgery/euth (64) – Euthanasia (64) – Chemotherapy (28) – Surgery/chemo (3) – Chemo/euth (22) – Chemo/surgery (3) – No Rx (2) Feline (157 cases) – Surgery (105)(67%) – Surgery/euth (18) – Euthanasia (21) – Chemotherapy (2) – Surgery/chemo (1) – Chemo/euth (8) – Surg/chemo/euth (2)

26. Results – Cost breakdown Canine – $0-499 (145 cases) – $500-999 (209 cases) – $1000 – 1499 (167 cases) – $1500-$1999 (103 cases) – $2000+ (94 cases) – ($9784 – primary brain tumor) Feline – $0-499 (46 cases) – $500-999 (55 cases) – $1000 – 1499 (29 cases) – $1500-$1999 (22 cases) – $2000+ (5 cases)

27. “Here, gentlemen, a dog teaches us a lesson in humanity” ( Napolean Bonaparte)

28. Why study dogs? Dogs are the only species of animal, besides man, in which there is a high incidence of spontaneous primary brain tumors (as just one example) Dogs share the human environment and “lifestyle” Dogs are of sizes approximating humans, display cognitive functions and learning, and are long-lived in comparison to other species Dogs with tumors, and their owners, suffer and need workable therapies

29. Transitional cell carcinoma (TCC)

30. A malignancy of the urinary bladder and kidney that is more common in Scottish breed terriers (Scottish Terriers, West Highland White Terriers) than other breeds of dog Signs: loss of housebreaking, frequent attempts to urinate, blood in urine and/or foul smell, vocalization, inconsistent urination, abdominal pain, palpable mass (+/-)

31. TCC facts TCC represents 1.2-2.0% of all canine cancers The incidence of TCC increased 600% between 1975-1995 in dogs

32. TCC risk Mixed breed dogs – risk of 1.0x (baseline) Scottish Terriers – 18.0 x (more than mixed breed dogs) Shetland Sheepdogs – 4.5 x Wire-haired terriers – 3.2 x West Highland White Terriers – 3.0 x

33. Urinary bladder TCC

35. CT study of TCC in urinary bladder

36. TCC and lawn chemicals? “Herbicide exposure and the risk of transitional cell carcinoma of the urinary bladder in Scottish Terriers,” Glickman, LT, Raghavan, M, Knapp, DW, Bonney, PL, Dawson, MH, Journ Amer Vet Med Assoc 24:1290-1297, 2004

37. TCC and lawn chemicals? Studied 83 Scotties with TCC and 83 Scotties without TCC but with other medical conditions Retrospective analysis of medical record and exposure data (1991 – 2,4 dichlorophenoxyacetic acid [2,4,D] – lymphoma in dogs and people)

38. 2,4 D (dichlorophenoxyacetic acid) Decreases synthesis of RNase – helps clean up damaged genome Uncouples oxidative phosphorylation – critical for cell metabolism Increases hepatic peroxysome synthesis – transformation of drugs and chemicals

39. Odds ratios of development of TCC in Scottish Terriers Herbicides and insecticides - 7.19 Phenoxyherbicides – 4.42 Herbicides – 3.62 Non-phenoxyherbicides – 3.49 Insecticides – 1.62 Affected (mutated) genes in Scotties not yet known

40. How do we stop the cancer epidemic in our dogs? Understand risk factors ( breeds, age) (Breed Genetics Study) Understand clinical signs Early detection (CKA, gene array, proteomics) (Need Westie Tissue and Serum Bank) Early intervention Research to find out the why (genetics, genomics, triggers)

42. John Robertson VMD PhD Director of the Center for Comparative Oncology (CeCO) Professor of Pathology, VA-MD Regional College of Veterinary Medicine (VMRCVM) Co-author of Westie Health E-Book

43. The Center for Comparative Oncology