Feline mammary carcinomas are one of the most common neoplasms affecting middle-aged and older female cats of all breeds. Because most feline mammary tumours are malignant, early detection and aggressive therapy have a significant influence on survival time. The percentage of malignant mammary tumours is higher in the cat (86%) than in the dog (42%), and the histology of feline mammary tumours is closer to that in human breast cancer.
The incidence and the morbidity of these tumours has been demonstrated to be very high because their biologic behaviour is characterized by rapid growth, high proliferation rates, and capability to metastasize to regional lymph nodes and distant organs.
An association between development of mammary tumours and use of progestins has been reported many times in the literature.
The interval between feline mammary carcinoma (FMC) detection and death varies from <6 to 12 months. Several factors, including age, diameter of the primary lesion, the presence of histologically tumour-positive lymph nodes, mitotic count, extent of necrosis, and complete surgical excision, are independently correlated with post-surgery survival time. A radical surgical treatment instead of a conservative one is significantly related to the disease-free interval.
Mammary tumors in cats are most common in older (average 11 yr) intact females. The use of megestrol acetate (Ovarid) has been incriminated as a potential trigger for development of mammary tumours. Spaying at an early age, especially before the first oestrus, has a sparing effect and reduces the risk, but the degree of protection is less precisely documented than that for dogs. The two anterior or thoracic glands are more frequently involved than the posterior glands.
Histologically, most feline mammary tumors are adenocarcinomas, with tubular or papillary types more common than solid or mucoid types. Mixed mammary tumors and sarcomas are less commonly diagnosed than carcinomas. Benign tumors of the feline mammary gland are relatively infrequent and account for only ~10% of these tumors.
The etiology of feline mammary tumors remains poorly defined, but several known risk factors have been recognized. Both Siamese and Persian cats appear to develop mammary neoplasia frequently, representing up to 34% and 16% of the affected population, respectively. 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.
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. 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.
In addition to progesterone, intact sexual status also influences the incidence of mammary tumor development, with early ovariohysterectomy providing a protective effect. 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. However, spaying after two years of age does not alter the risk of developing mammary tumors, and parity has no effect.
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. 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%). However, PR expression is variable in normal tissues as well as in benign lesions and malignant mammary carcinomas. 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. 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.
Because feline mammary tumors generally behave aggressively, identifying HER2 overexpression in these tumors may account for the poor prognosis associated with this tumor type. Recent investigations have demonstrated HER2 expression to be low (25%) in benign mammary tumors and absent in nontumor samples. In contrast, 41% to 90% of feline mammary carcinomas express HER2.
In addition to its identification in mammary carcinomas, HER2 expression appears prognostic for survival time. Queens with greater HER2 expression treated with surgery alone had a shorter median survival time (14.6 months) than HER2-negative queens (18.7 months). Interestingly, HER2 was not correlated with histologic subtype, tumor grade, or lymphatic invasion, suggesting that HER2 expression may serve as a prognostic variable independent of other histologic criteria in cats with mammary tumors.
- Feline mammary hypertrophy
A distinct entity called feline mammary hypertrophy or fibroadenomatous hyperplasia has been noted in cats. It affects primarily young, actively cycling, or pregnant cats. It also has been seen in neutered cats, including older males given exogenous progestational drugs (megestrol acetate). The disorder is marked clinically by the rapid growth of one or more mammary glands. This benign condition is characterized by rapid abnormal growth of one or more mammary glands. There are 2 basic types of hyperplasia of the feline mammary gland—lobular hyperplasia and fibroepithelial hyperplasia. Lobular hyperplasia is seen as palpable masses in one or more mammary glands in intact cats 1-14 yr old. Fibroepithelial hyperplasia occurs in young, cycling, or pregnant cats; in old, intact females and males; and in neutered males after treatment with progestins. Feline mammary hypertrophy is considered to be a hormone-dependent dysplastic change in the mammary gland. Hyperplasia occurs within 1-2 wk after oestrus or 2-6 wk after progestin treatment. The tremendously enlarged glands may appear erythematous, and some of the skin may be necrotic. Oedema of the skin and both hind legs is common, and the condition can easily be confused with acute mastitis. Ovariohysterectomy or mastectomy is curative, although spontaneous remissions occur. Ovariohysterectomy is followed by regression of the glands and prevents recurrence.
A mammary tumour is usually suspected on detection of a mass during physical examination. The length of time the mass has been present is usually unknown, but the rate of growth may be helpful in determining prognosis. Palpation of the regional lymph nodes can help determine the extent of spread. Thoracic radiographs, preferably 3 views (a ventral-dorsal and 2 laterals), should be taken to detect pulmonary metastases. Fine-needle aspirates may differentiate between inflammatory and neoplastic lesions but may lead to erroneous conclusions and delay of surgery. The diagnosis is determined by histopathology and is important in defining treatment and prognosis.
About 90% of feline mammary tumors are malignant. Most are carcinomas or adenocarcinomas, with the most common histologic patterns being tubular, papillary, and solid carcinomas. Tumors are graded as well-differentiated (Grade I), moderately differentiated (Grade II), and poorly differentiated (Grade III) based on histologic features including tubule formation, nuclear and cellular atypia, and mitotic index. Histologically, invasion into the lymphatic or vascular system or both is common—noted in 27% to 57% of tumor samples. Additionally, infiltration of cancer cells into the surrounding stroma occurs at an even greater frequency, with a reported rate of 42% to 88%. Although most feline mammary tumors are of epithelial origin, malignant transformation may occur in mesenchymal tissues resulting in the development of mixed mammary tumors and sarcomas.
Mammary tumors are treated surgically, although there is no consensus as to the best procedure. Removal of the tumour alone (lumpectomy), simple mastectomy (removal of the affected gland only), modified radical mastectomy (removal of the affected gland and those that share lymphatic drainage and associated lymph nodes), and radical mastectomy (removal of the entire mammary chain and associated lymph nodes) all have their proponents. In dogs, the more involved procedures have not prolonged survival compared with the others, and the advantages of the simpler procedures are obvious. In cats, radical mastectomy has increased the disease-free interval but not survival time.
In theory, the use of anticancer drugs to combat micrometastatic disease (adjuvant chemotherapy) is a reasonable consideration. However, chemotherapy has not been proved an effective treatment for mammary tumors in dogs. Part of the difficulty of evaluating the response to adjuvant chemotherapy relates to the fact that only about half of the canine mammary tumors diagnosed as malignant on histopathologic examination actually behave that way. A combination of doxorubicin and cyclophosphamide has been used with limited efficacy in cats. Neither radiation therapy nor anti-estrogenic compounds have been effective.
The prognosis is based on multiple factors. Most mammary tumors in dogs that are going to cause death do so within 1 yr. Sarcomas are associated with shorter survival times than carcinomas. Other factors, including size of tumour, lymph node involvement, and nuclear differentiation, also affect the prognosis. In cats, tumor size is important; cats with tumors >3 cm in diameter have a median survival time of 6 mo, but cats with tumors <2 cm in diameter have a median survival time of >4 yr.
- ↑ M Dolores Pérez-Alenza,1 Ángeles Jiménez,1 Ana I Nieto,1 and Laura Peña (2004) First description of feline inflammatory mammary carcinoma: clinicopathological and immunohistochemical characteristics of three cases. Breast Cancer Res 6(4):R300–R307
- ↑ Gimenez, F (2010) Early detection, aggressive therapy: Optimising the management of feline mammary masses. JFMS 12:214-224
- ↑ Hahn KA, Adams WH. (1997) Feline mammary neoplasia: biological behaviour, diagnosis and treatment alternatives. Feline Pract 25:5–11
- ↑ Misdorp W, Else RW, Helmén E, Lipscomb TP. (1999) Histological Classification of Mammary Tumors of the Dog and Cat. Washington: Armed Forces Institute of Pathology and World Health Organization
- ↑ Jacobs, TM et al (2010) Mammary adenocarcinomas in three male cats exposed to medroxyprogesterone acetate (1990-2006). JFMS 12:169-174
- ↑ Merck Veterinary Manual
- ↑ F. Millanta, et al
- ↑ Skorupski, KA et al (2005) Clinical characteristics of mammary carcinoma in male cats. J Vet Int Med 19:52-55
- ↑ Mol, JA et al (1996) New insights in the molecular mechanism of progestin-induced proliferation of mammary epithelium: induction of the local biosynthesis of growth hormone (GH) in the mammary gland of dogs, cats and humans. J Steroid Biochem Mol Biol 57:67-71
- ↑ Hahn, KA, Bravo, L & Avenell, JS (1994) Feline breast carcinoma as a pathologic and therapeutic model for human breast cancer. In Vitro 8:825-828
- ↑ Hahn, KA & Adams, WH (1997) Feline mammary neoplasia: biological behaviour, diagnosis and treatment alternatives. Feline Pract 25:5-11