Incidence, Causes, and Pathogenesis

The true incidence of mammary tumor development in dogs is difficult to determine since many small or benign-appearing tumors may go untreated and thus unreported. However, an insurance population study of female dogs in Sweden reported 111 mammary tumor claims per 10,000 dog-years at risk. Prior reports indicated that the annual incidence of canine mammary tumors (CMTs) in the United States approximates 200 per 100,000 dogs at risk. Breeds reported to be at increased risk include English springer spaniels, Brittany spaniels, cocker spaniels, toy and miniature poodles, English setters, pointers, German shepherds, Maltese, Yorkshire terriers, and dachshunds. Mammary tumors most commonly affect middle-aged (9 to 11 years) female dogs, with an increased incidence beginning at approximately 6 years of age. The influence of hormones on CMT development is supported by the early work showing that the risk of developing mammary tumors rises to 26% for dogs spayed after their second estrus, compared with 0.5% and 8% for dogs spayed before their first or second estrus, respectively. It is thought that sex steroid hormones have their primary effect on target cells during the early stages of mammary carcinogenesis, which accounts for the lack of protective effect with spaying beyond two estrous cycles. The use of products containing medroxyprogesterone acetate (progestin and estrogen combination) for the prevention of estrus or to treat pseudopregnancy has also been linked to an increased incidence of CMTs. Although CMTs are primarily a disease of female dogs, approximately 1% of CMTs are in males and can be associated with hormonal abnormalities such as estrogen secretion by a Sertoli cell tumor. Other factors reportedly associated with an increased risk of CMT development include obesity at a young age and feeding of homemade diets as opposed to commercial foods.

Clinical Presentation

Mammary tumors often are detected during routine wellness examinations in older female dogs or are discovered by conscientious owners. The median age of onset for benign tumors is reported to be lower than that for malignant tumors (8.5 years versus 9.5 years, respectively). In over half of all cases, dogs have more than one mammary mass at presentation; these may be simultaneous primary masses or may represent one primary lesion with regional extension or metastasis. Although some studies have suggested that the caudal mammary glands are the most commonly affected in the dog, other reports have not confirmed this. Either the axillary or inguinal lymph nodes may be palpably enlarged in dogs with nodal metastases, given the complex pattern of lymphatic drainage for canine mammary tissue. There are five pairs of mammary glands in the dog (two cranial-thoracic, two abdominal, and one caudal-inguinal). The thoracic glands generally drain to the axillary or sternal nodes, the inguinal glands drain to the inguinal nodes, and the two abdominal glands may drain to either site. The presence of lymph node enlargement, lymphedema, skin ulceration, and fixation to underlying tissue are characteristics that suggest malignancy.

Inflammatory mammary carcinoma (IMC) is a unique clinical entity that warrants an altered approach to diagnosis and case management. This tumor type may be mistaken for mastitis since affected dogs classically have warm, erythematous mammary tissue and associated lymphedema; ulceration and vesicles; and significant pain on any manipulation of the tissue. Alternatively, the diagnosis of IMC may become apparent when wound dehiscence occurs secondary to what was anticipated to be a routine mammary mass excision (referred to as secondary IMC).

Diagnosis and Staging

The diagnosis of CMTs relies on histologic examination of incisional or excisional biopsy samples. Fine-needle aspiration and cytologic examination of mammary nodules is recommended by some because it may help differentiate preoperatively between benign and malignant masses and between CMT and other tumors (such as mast cell tumor) or nonneoplastic lesions. However, a 2007 study showed that one in four cytologic specimens from CMT contain inadequate cellularity to be of diagnostic value; thus histopathologic analysis still is considered to be imperative for diagnosing CMT (Cassali et al, 2007). It is vital to bear in mind that benign and malignant nodules may coexist in canine mammary tissue. Therefore it is necessary to confirm the histologic diagnosis independently for each nodule rather than assume that one nodule is representative of all tumors present. Estimates vary in the literature, but a simple rule of thumb for CMTs is that approximately 50% are malignant and approximately 50% of the malignant tumors metastasize. Of these, sarcomas and IMCs are associated with the worst prognosis. Mixed malignant tumors and squamous cell carcinomas also are associated with poor survival times. Of the carcinomas, solid carcinomas are reported to have worse survival times than either tubular or papillary carcinomas. Carcinomas that have a better prognosis include carcinoma in situ and adenocarcinomas.

The original clinical staging for CMTs was based on a four-stage system developed by the World Health Organization (WHO) and reported in 1980. Since that time, a modified staging system has been reported and is described in Table 84-1. The primary differences are the addition of a stage V for dogs with distant metastatic disease and the designation of a stage IV (rather than stage II or III) for those with nodal metastasis. Either staging system necessitates evaluation of regional lymph nodes and assessment of potential distant sites of metastasis, especially distant lymph nodes and lungs. Preoperative cytologic examination of any palpable lymph nodes may aid in determining disease extent before surgery. Regardless of preoperative assessment, lymph node tissue removed at the time of surgery should be submitted for histologic examination. Although standard hematoxylin and eosin (H&E) staining of slides from nodal tissue permits accurate identification of micrometastasis in most cases, cytokeratin immunostaining using an antipancytokeratin antibody AE1/AE3 was reported to detect occult micrometastasis in 12 of 131 lymph nodes (9.2%) from dogs judged to have node-negative disease based on H&E results (Matos et al, 2006). The impact of the presence of micrometastatic disease on the prognosis for CMT is unknown at this time. Obtaining three-view thoracic radiographs before surgery is essential because pulmonary metastases are associated with a poor prognosis and may alter therapy decisions.

In addition to clinical staging, there is a histologic staging system outlined in Table 84-2. In this system stages 0, I, and II are based on histologic assessment, whereas stage III is based on clinical assessment of distant metastasis. This system is not to be confused with the clinical staging systems proposed in Table 84-1. Although the histologic staging system is not universally applied in veterinary medicine, it is highlighted in this chapter because of its correlation with clinical outcome in a report of 232 dogs undergoing mastectomy for CMTs.