Transitional cell carcinoma in Scottish breed terriers ..

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Dealing with cancer in dogs What this means to
you and your Westie

• John Robertson VMD PhD
• Center for Comparative Oncology, Virginia Tech

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Warning! This presentation contains a few
pictures of cats and other critters
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Whats this talk about?

• Tumors, neoplasms, cancer whats 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?

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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

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Multicentric melanoma Arabian Horse
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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)

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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!

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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)

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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,
  3rd ed., 2005)

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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

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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)

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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

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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

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Review of VMRCVM oncology medical records
2004-2006
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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)

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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)

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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)

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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)

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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)

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Here, gentlemen, a dog teaches us a lesson in
humanity(Napolean Bonaparte)
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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

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Transitional cell carcinoma (TCC)
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Transitional cell carcinoma (TCC)

• 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 (/-)

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TCC facts

• TCC represents 1.2-2.0 of all canine cancers
• The incidence of TCC increased 600 between
  1975-1995 in dogs

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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

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Urinary bladder TCC
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CT study of TCC in urinary bladder
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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
  241290-1297, 2004

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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)

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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

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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

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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)

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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

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The Center for Comparative Oncology