Malignant mammary tumors: Biologic behavior, prognostic factors, and therapeutic approach in cats - Veterinary Medicine
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Malignant mammary tumors: Biologic behavior, prognostic factors, and therapeutic approach in cats
Most mammary tumors in cats are malignant, and metastasis is common. The prognosis depends on how far the cancer has spread and the tumor's biologic behavior, among other things. Find out how to improve the outcome in these critically ill cats.


VETERINARY MEDICINE


ETIOLOGY AND RISK FACTORS


Table 1 Risk Factors for Mammary Cancer in Cats
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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