PATHOPHYSIOLOGY

General Considerations

•mammary tumors are the 3rd most common tumor in cats and account for 17% of all tumors in female cats

•breed predisposition: DSH and Siamese

•mean age 10-12 years (range, 9 months to 23 years)

•Siamese cats are associated with mammary tumors at a younger age and higher rate of lymphatic invasion

Benign Mammary Conditions

•15% of feline mammary tumors are either benign or dysplastic

•3 types of non-inflammatory hyperplasia: ductular, lobular, and fibroepithelial hyperplasia

•fibroepithelial hyperplasia diagnosed in cats after silent estrous, during pregnancy, and treated with exogenous progestins

•majority of cats < 2 years

•multiple mammary gland involvement is more common than involvement of 1 mammary gland

•massive glandular involvement can be seen due to hormonal stimulation of glandular tissue

•edema of skin and subcutaneous tissue common and can result in erythema and skin necrosis

•systemic infection and pulmonary embolism have been reported

•benign mammary tumors include simple and complex adenoma, fibroadenoma, and ductal papilloma

Malignant Mammary Tumors

•mammary tumors in cats are usually malignant (85%-93%)

•80% of feline mammary tumors are ADC with tubular, papillary, solid, and cribriform subtypes most common

•sarcoma, SCC, and mucinous carcinoma subtypes are less common

•invasion, ulceration, lymphatic invasion, and lymph node metastasis is common

•> 80% have metastasis at euthanasia

•metastatic sites: lymph nodes, lungs, pleura, liver, diaphragm, adrenal glands, bone, and kidneys

•skeletal metastasis is more common to distal extremities rather than proximal to elbow or stifle as in dogs

Ovariohysterectomy and Hormones

•intact queens have a 7-fold higher risk of mammary cancer than spayed female cats

•ovariohysterectomy, regardless of age, results in 40%-60% reduced risk of developing mammary tumors compared to intact queens

•exogenous progestins or combination of estrogen-progestin is associated with 3-fold risk of developing either benign or malignant mammary tumors

•benign fibroepithelial hyperplasia may also be caused by administration of sex steroids

•estrogen receptors are rare in cats but progesterone receptors are common in benign tumors

•malignant tumors lose steroid dependence during malignant progression and have less frequent expression of estrogen and progesterone receptors

•role of growth hormone unknown, but mammary tissue from fibroepithelial hyperplasia and malignant tumors express growth hormone in the absence of progesterone receptors indicating possible autonomous growth and hormone production

CLINICAL FEATURES

Clinical Signs

•mammary tumors frequently adhere to overlying skin but not the abdominal wall

•ulceration is common

•nipples red and swollen and exude tan to yellow fluid

•no site or side predilection with all mammary glands equally affected

•multiple gland involvement observed in > 50% cases

•lung and pleural metastasis may be extensive and cause respiratory insufficiency due to pleural carcinomatosis and effusion

Diagnosis

General Considerations

•physical and rectal examination to assess extent of disease

•lymph node metastasis is present histologically in 49% cats, but only 21% of lymph nodes are clinically palpable

•hematology and serum biochemistry

•coagulation profile is recommended for cats with suspected malignant tumors due to the risk of DIC

•FNA but difficult to differentiate benign and malignant mammary tumors

•FNA is useful in the diagnosis of inflammatory carcinoma and metastatic mammary tumors to regional lymph node

•thoracocentesis if pleural effusion present

•thoracic radiographs: metastatic disease appear as interstitial densities

•caudal abdominal radiographs or ultrasonography for sublumbar lymph node metastasis

•biopsy if inflammatory carcinoma suspected

Clinical Staging

TREATMENT

Medical Management

Chemotherapy

•short-term PR observed in 64% (9/14) cats with doxorubicin alone with MST for non-responders 6 months and responders 8 months

•short-term PR observed in 50% (7/14) cats with doxorubicin and cyclophosphamide with MST for non-responders 2.5 months and responders 5 months

Hormonal Therapy

•anti-progestins may be an effective alternative for the management of fibroepithelial hyperplasia

Surgical Management

•radical mastectomy is recommended, regardless of tumor size, with en bloc removal of adhered tissue due to invasive nature and to reduce risk of recurrence

•bilateral mastectomy can either be performed simultaneously or staged by 2-6 weeks

•glands 1 and 2 have common lymphatic drainage into the axillary and then sternal lymph nodes

•glands 3 and 4 drain into inguinal lymph nodes

•inguinal lymph node or axillary lymph node removed if enlarged or cytologic evidence of metastasis

•ovariohysterectomy does not decrease rate of local tumor recurrence but causes gradual regression of fibroepithelial hyperplasia

PROGNOSIS

General Considerations

•prognosis is guarded to poor with tumor-related deaths in most cats within 10-12 months

•overall median DFI 341 days and MST 428 days

•poor prognostic factors: tumor size, extent of surgery, and histologic grading

Tumor Size

•tumor size is the single most important prognostic factor in feline mammary tumors

Clinical Stage

Histologic Features

•degree of nuclear differentiation: well-differentiated tumors are rare but associated with increased survival time

•well differentiated: 13% prevalence and 100% 12-month survival rate

•moderately differentiated: 60% prevalence and 42% 12-month survival rate

•poorly differentiated: 27% prevalence and 0% 12-month survival rate

•MST for tumors with local invasion only is 21.8 months v 13.4 months for tumors with blood vessel or lymphatic invasion

•tumors with a low mitotic index have a significantly better MST than high mitotic index (22.4 months v 12.4 months)

Proliferation Indices

•high proliferation index with Ki-67 associated with decreased survival time in cats with mammary carcinoma, with:

•12-month survival rate with high proliferative index 12% v 88%

•AgNOR counts is prognostic in cats with MST significantly better with low AgNOR counts (21.9 months v 13.8 months)

Other

•radical mastectomy increases DFI (1,200 days v 300 days) but no significant effect on survival time

•however, radical mastectomy has been shown to significantly improve survival time in other studies:

•MST 917 days for bilateral mastectomy

•MST 566 days for unilateral mastectomy

•MST 216 days for subtotal mastectomy

From: Withrow SJ & MacEwen EG (eds): Small Animal Clinical Oncology (3rd ed).

•lymph node involvement significantly decreases MST (6 months v 18 months)