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Vol. 05 Issue 2, Spring 2000

Research Commentary: Using Comparative Cancer Models for Breast Cancer Research
The Ribbon 

Szabo CI, Wagner LA, Francisco LV, Roach JC, Argonza R, King MC, Ostrander EA. (Fred Hutchinson Cancer Research Center and University of Washington, Seattle) Human Molecular Genetics 5:1289-1298, 1996.

The role of comparative cancer research in the effort to reduce the morbidity and mortality of cancer in humans is evolving rapidly. Rodent models of human cancer are essential for investigation of numerous in vivo issues. In most cases, however, data from rodent studies must be extrapolated to humans with caution and some technologies are not easily studied in small animal models. Investigation of cancer in companion animals (dogs and cats) offers significant advantages to the research community because of similarity in cancer etiology, repeated access to normal and tumor tissue during a study and clinically relevant treatment outcomes. Many academic and pharmaceutical cancer research institutions are now supporting investigations in companion animal cancer as one component in a complementary array of preclinical models. Such investigations are clearly done to advance human health but animal health has advanced substantially as a result.

Breast cancer is the most common malignancy in female dogs (estimated incidence = 175/100,000 dogs at risk but risk in sexually intact dogs is approximately 260/100,000). Canine breast cancer is similar to breast cancer in women in several ways: 1) 95% of cancer arises from the glandular epithelial tissue, 2) approximately 35-45% of cancers express estrogen and/or progesterone receptors and such expression represents a favorable outcome, and 3) aggressive clinical behavior occurs in approximately 25% of dogs with breast cancer including regional and widespread metastases.

Based on the report of Szabo, et al, cited above, canine breast cancer is now known to be genetically similar to breast cancer in women. These investigators identified and compared the nucleic acid and protein sequence of the BRCA1 homolog in dogs and mice. In all three species the BRCA1 gene codes for a protein of between 1850-1900 amino acids which may function as a tumor suppressor.

In addition to similarities in general structure, the sites of missense gene alterations known to account for exceptionally high rates of breast cancer in women occur in highly conserved regions of the gene in both the dog and rodent.

It is estimated that 5-10% of breast cancer in women may be attributed to inheritance of mutations in the BRCA1 gene. The role of BRCA1 mutations in dogs is unknown and to date no mutations in the BRCA1 gene have been identified in breast cancer of dogs. However, inheritance of canine breast cancer has been suggested by several studies and identification of canine families with strong heritable tendencies of breast cancer would be valuable. Since pedigree and breeding information is recorded for many purebred dogs and because this is a spontaneously occurring, frequent tumor, investigating the significance of this gene in breast cancer development may be more relevant in dogs than in rodents.

As the canine and feline genome are resolved, many genetically based diseases such as cancer are found to be etiologically similar across species lines. Many tumor suppressor genes and oncogenes in dogs and cats are strongly conserved in the regions where functional mutations occur in human cancer. Furthermore, environmental exposure of carcinogens has been documented to increase the risk of various cancers in dogs. It seems obvious that such a relevant and prevalent resource should be more aggressively incorporated into cancer control programs. Currently, however, this resource is vastly underutilized. Development of tumor registries, tumor depositories, comprehensive companion animal cancer centers and cooperative research endeavors are required to extend the phenomenonology of canine and feline cancer into clinically applicable programs for the investigation of prevention, early diagnosis and control of cancer for all species.

Prepared by:
Dr. R.L. Page, Director
The Comparative Cancer Program at Cornell University

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Last Update 08.23.00