Mammary tumor

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Clinically, mammary tumors often appear as tissue nodules or enlargements within the mammary glands[1]
An invasive mammary carcinoma in a dog, with environmental toxins implicated in this case[2]
Above dog, showing tumor after unilateral mastectomy[2]
Histologicasl appearance of a mixed mammary tumor from a dog that presented with paraneoplastic extramedullary hematopoiesis[3]

Mammary tumors are the most common neoplasm of the female dog and represent over 50% of all neoplasms in females over 8 years of age[4].

Of the mammary gland tumors diagnosed in female dogs, 40 - 50% are malignant[5]. These tumors are particularly common in many European countries where animals are not routinely spayed at a young age. although the incidence is not directly related to neutering[6].

The majority of malignant tumors arise from epithelial tissue and metastasize to the lungs, heart[7], spleen, liver, inguinal lymph nodes, brain[8] and bones[9].

A breed predisposition has been noted in female Shih Tzus[10] and male Cocker Spaniels[11]. In males, they are frequently benign adenomas.

The types of canine mammary tumors which can occur are numerous, although the majority of clinical presentations are malignant adenocarcinomas and carcinomas. Variants include:

The median age for diagnosis of mammary tumors in dogs is 10 years; neoplasms rarely occur in dogs <4 years of age[24]. At 6 years of age, the risk of developing a mammary tumor appears to increase markedly. It also appears that after 14 years of age, the incidence of benign mammary tumors levels off while the incidence of malignant cancer continues to increase[25]. In malignant cases, the 2-year survival is only about 25 - 40%[26]. Incidence increases with age: the median age of tumor manifestation is 10 to 11 years

The development of mammary gland neoplasms appears to be estrogen- and progesterone-dependent because the risk of developing a mammary tumor increases as the number of estrous (heat) cycles increases[27]. While steroid hormones are considered to be involved in early carcinogenesis, they seem to lose their stimulatory effect during progression of disease[28]. Most canine mammary tumors are also associated with a decline in prolactin receptor expression locally within the mammary tissue[29].

Breed predisposition in the development of mammary neoplasms has been reported but varies in different studies. Several of the spaniel breeds, poodles, and dachshunds have been reported to have an increased incidence of mammary neoplasia. Mammary gland tumors also have been observed in male dogs, but the incidence is 1% or less. Affected male dogs usually have a hormonal imbalance such as an estrogen-secreting Sertoli cell tumor of the testis[30].

Clinically affected dog usually present with single or multiple nodules within a mammary gland or chain, with associated lymphadenopathy. These nodules are present in >50% of dogs with mammary neoplasms. The majority of mammary gland tumors occur in glands 4 and 5 (60-70%), possibly due to the fact that the two most caudal pairs of glands contain the most mammary tissue.

Secondary dermal lesions may occur at the interface between tumor and skin, such as dermatitis, pyoderma and abscess formation.

Blood tests often reveal hypercalcemia[31]. In severe cases, secondary DIC is usually evident, based on biochemical changes such as thrombocytopenia, prolonged prothrombin, activated partial thromboplastin and thrombin times[32].

A number of paraneoplastic syndromes have been associated with these tumors, including hypoglycemia[33], peripheral vascular thromboembolism[34], myeloid metaplasia[35], extramedullary hematopoiesis[36], hyperparathyroidism[37], secondary polyneuropathy[38] and GH-producing tumors with secondary acromegaly[39].

Mammary carcinomas may exhibit rapid growth, doubling in size within a few weeks. However, the size and appearance of these neoplasms can vary greatly. Inflammatory carcinomas usually have diffuse involvement of multiple mammary glands. Edema, erythema, and firmness may be present and affected mammary glands may feel warm to the touch. Dogs with inflammatory carcinoma are more likely to have generalized weakness with anorexia and weight loss. Inflammatory carcinoma is often misdiagnosed as acute mastitis[40].

Mammary gland tumors are difficult to diagnose by routine mammary cytology. Furthermore, it can be very difficult to determine the malignant potential of mammary neoplasms cytologically, and histological evidence of malignancy does not always imply an aggressive clinical course of disease. Mammary hyperplasia, dysplasia, adenomas (benign neoplasms), and well differentiated carcinomas (malignant neoplasms) can have a variable morphologic appearances but evidence of T lymphocyte infiltration in the malignant group correlates significantly with a poor prognosis[41].

Histopathological diagnosis of canine mammary gland tumors is based on 'TNM' (T: size of the primary tumor, N: condition of the regional lymph nodes, and M: absence/presence of distant metastasis) staging[42][43].

Tumors are usually graded as grade I (29/65), grade II (19/65), and grade III (17/65). The tumor size, clinical stage, histological diagnosis, presence/absence of myoepithelial proliferation, and regional lymph node metastases at diagnosis are significantly associated with histological grade[44].

Treatment usually involves local surgical excision. There is no difference in recurrence rate or survival time when a simple versus a radical mastectomy is performed[45]. Also, it does not appear to be of benefit to spay the dog at the time of the mastectomy surgery.

Carboplatin has been reported as an effective conjunctive therapy in some canine patients[46] as well as gemcitabine[47] and post-operative use of combination drugs such as doxorubicin and docetaxel[48].

Other drugs which have been tested include anti-progesterone drugs such as aglepristone[49] and bovine lactoferrin[50].

Unfortunately, there is no reliable information on the value of radiation treatment, although it may be useful in dogs that have tumors that are too extensive for surgery.

Because COX-2 expression and survival are closely related in canine mammary tumors[51], the use of NAIDs such as tolfenamic acid may be indicated and have been shown to improve survival rates in some dogs[52].

Overall survival rates are good in dogs, depending on time of detection.

References

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  3. Grandi F et al (2010) Extramedullary hematopoiesis in a case of benign mixed mammary tumor in a female dog: cytological and histopathological assessment. BMC Vet Res 6:45
  4. Merlo DF et al (2008) Cancer incidence in pet dogs: findings of the Animal Tumor Registry of Genoa, Italy. J Vet Intern Med 22(4):976-984
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