ETIOLOGY AND RISK FACTORS
Table 1 Risk Factors for Mammary Cancer in Cats
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The etiology of feline mammary tumors remains poorly defined, but several known risk factors have been recognized (Table 1).
Biological carcinogens
Biological carcinogens, such as viruses, have been evaluated in feline mammary tissues. Although viral particles have been
identified within the tissues, their presence has not been directly linked with tumor development.24,25
Genetic factors
Familial or genetic predispositions for developing feline mammary carcinoma have also been investigated. Both Siamese and
Persian cats appear to develop mammary neoplasia frequently, representing up to 34% and 16% of the affected population, respectively.7,16,26,27 In addition to Siamese cats being overrepresented, mammary neoplasia appears to occur at a younger age (9 years for Siamese
vs. 14 years for non-Siamese) in this popular Oriental breed.6
Sex hormones
The role of sex hormones in mammary neoplasia development remains to be clearly elucidated, but several studies underscore
the probable involvement of estrogen and progesterone in mammary gland tumorigenesis. Long-term progestin administration and
endogenous progesterone increase the risk of both benign and malignant mammary tumor development, while intermittent or occasional
progestin administration has no effect.5,11,28,29 Furthermore, although the relevance to tumor development could not be determined in a recent clinical evaluation, eight
of 22 male cats with mammary tumors were reported to have received progestin treatments.10
Reproductive status
In addition to progesterone, intact sexual status also influences the incidence of mammary tumor development, with early ovariohysterectomy
providing a protective effect.6,28 A recent study showed that intact cats were 2.7 times more likely to develop mammary carcinoma, and the age of queens at
neutering was important. Spaying before 6 months, 12 months, and 24 months of age results in a 91%, 86%, and 11% risk reduction
in mammary tumor development, respectively.30 However, spaying after two years of age does not alter the risk of developing mammary tumors, and parity has no effect.11,30
Estrogen and progesterone receptor expression
Estrogen receptor (ER) and progesterone receptor (PR) expressions in mammary carcinomas are routinely evaluated in human breast
cancer patients, with ER- and PR-positive tumors being associated with a more favorable prognosis. Almost one in eight women
will develop breast cancer, and it is the second-leading cause of cancer death in women.31
Given the biologic similarities of human and feline breast carcinomas, recent studies have investigated ER and PR status in
feline mammary tumors. Compared with 76% ER expression in normal tissue and 25% to 40% ER expression in dysplastic and benign
tumors, feline mammary carcinomas are predominantly ER-negative (56% to 90%).31-33 However, PR expression is variable in normal tissues as well as in benign lesions and malignant mammary carcinomas.33-35 Collectively, these findings demonstrate that ER and PR expression varies in feline mammary carcinomas, perhaps reflecting
the undifferentiated state and, hence, aggressive biologic behavior of mammary tumors in cats.
HER2 expression
In human breast carcinoma, the human epidermal growth factor receptor 2 gene (HER2/neu) is overexpressed in 10% to 40% of patients.23 This overexpression of the HER2 receptor is permissive for uncontrolled cell growth and facilitates tumor development. In
human breast carcinoma patients, increased HER2 expression confers a poor prognosis and may predict limited response to hormonal
therapy. The overexpression of the HER2 protein is variable in canine mammary tumors (37% to 73% positive) but confers a poor
prognosis.36,37
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