Mammary gland tumors remain one of the most common cancers in our canine patients. Despite the high incidence, there have been few significant advances in the treatment of these tumors. In this article, I review the current standard of care and present new insights into the biology of these tumors.

Biologic behavior

In dogs, the biologic behavior of mammary gland tumors is highly variable. The rule of thumb has been that 50 percent of mammary gland tumors are benign, and of the 50 percent that are malignant, half can be cured by surgery alone. This means that 25 percent of patients are at high risk of metastasis and require therapy beyond surgery alone.

For those dogs that do develop mammary tumors, it has been shown that up to 60 percent will develop multiple tumors, and dogs that have had a malignant tumor are at higher risk of developing a second malignant tumor compared with dogs with benign tumors. However, these separate primary tumors likely share a common etiology. It has been suggested that mammary tumors in dogs develop as a result of a phenomenon known as field carcinogenesis, which involves the idea that multiple tumors are the result of all of the mammary tissue being exposed to the same hormonal environment.

Prognostic factors

Well-known prognostic factors include tumor size, tumor type, grade of tumor, degree of differentiation, stage and the presence of vascular or lymphatic invasion. Equally important to note, factors that have not been shown to be prognostic include tumor location, number of tumors or the type of surgery performed.

Most studies have shown that tumors 3 cm or less have a better prognosis, although a recent study showed the same to be true of tumors up to 5 cm.¹ In this study, tumors > 5 cm were more likely to be associated with nodal metastasis, as were tumors that were present less than six months before surgery. Results also indicated that an OHE performed at the time of tumor removal significantly improved the two-year survival rate. These findings indicate that while tumor size is an important prognostic factor, it is necessary to look at other variables when estimating survival times.

Tumor types that have a negative prognosis include mammary gland sarcomas and inflammatory mammary gland tumors. Mammary gland sarcomas (fibrosarcoma or osteosarcoma) are uncommon but have been reported. The average survival time for mammary gland sarcomas of any kind is short, usually between 9 and 12 months. Inflammatory mammary gland tumors are highly aggressive and typically present as a rapidly growing tumor with ulceration, edema and erythema. On histopathologic examination, these tumors are poorly differentiated, with invasion of dermal lymphatics. Treatment typically consists of palliative care only, and the survival time for these patients is one to two months. Surgery is not recommended for patients with this tumor type.

Tumor grade has also been used as a prognostic indicator. Tumors that are classified as high grade have a high mitotic index, poor nuclear differentiation and significant necrosis. However, pathologists have not adopted a standard grading scheme for mammary tumors, so often the grade must be inferred from the microscopic description.

In addition, other molecular factors such as estrogen and progesterone receptor status, proliferative indices and the presence of certain gene mutations can predict biologic behavior. These factors have advanced our understanding of the biologic behavior and progression of mammary gland tumors but are not widely available for use in routine evaluation of clinical patients. In a recent study, 113 dogs with both malignant and benign mammary tumors were evaluated for the presence of estrogen and progesterone receptors.² Almost all of the benign tumors had both estrogen and progesterone receptors, but in the malignant tumors, only 50 percent had estrogen receptors and 70 percent had progesterone receptors. Tumors that were positive for both types of receptors were more likely to be < 5 cm and were less likely to have metastasized at the time of diagnosis. Particularly, the dogs that had the highest one-year survival rate were the dogs that were positive for progesterone receptors. The results of this study suggest that determining the presence of these hormone receptors may help predict tumor behavior.