Mammary tumors are common in dogs and are the most common type of neoplasia in sexually intact females. Mammary tumors are usually detected on physical examination. Surgical excision provides for histopathological diagnosis and locoregional control. Due to risk of metastasis, clinical staging is recommended prior to initiating treatment.
Mammary tumors are common in dogs and are the most common type of neoplasia in sexually intact females. In dogs, approximately half of mammary tumors are malignant.
Histopathological Tumor Types of Mammary Tumors in Dogs
Mammary tumors represent a diverse histopathological group in which approximately 50% are benign and 50% malignant. The following comprises a complete list of the various malignant histological types.
Most malignant tumors have a significant epithelial component. Tumors with only one epithelial cell population are classified as simple carcinomas of various subtypes and include tubular, cribriform, tubulopapillary, cystic papillary carcinomas. In addition, there are other types of carcinomas, such as micropapillary invasive carcinomas, solid carcinomas, comedocarcinomas, and anaplastic carcinomas.
Inflammatory carcinomas represent a uniquely aggressive subtype of carcinomas; histopathologically, these tumors are often anaplastic carcinomas but are characterized by extensive dermal lymphatic invasion, diffuse dissemination, inflammation, redness, swelling, and pain. The clinical picture may sometimes be mistaken for mastitis.
Another subgroup of tumors consists of more than one cell type; here, both epithelial and myoepithelial components are seen. This group is represented by carcinomas arising in a complex adenoma/mixed tumor, complex carcinomas, ductal carcinomas, and intraductal papillary carcinomas. In addition, carcinosarcomas or malignant mixed tumors (composed of epithelial and mesenchymal cell types, both of which are malignant) and malignant mesenchymal tumors (osteosarcomas, chondrosarcomas, fibrosarcomas, and hemangiosarcoma) may occur, but are relatively uncommon.
The prognosis varies across these tumor types and ranges from a relatively low risk of recurrence as seen in dogs with complex carcinomas (96% with 2-year survival) to very short survival in dogs with anaplastic carcinomas, and carcinosarcomas (0% with 1-year survival) (1). However, histopathologic subtype by itself does not provide an accurate prognosis; other factors such as grade, stage, and presence of vascular invasion all play important roles (2).
Pathogenesis
Risk Factors for Mammary Tumors in Dogs
Prolonged exposure to estrogens and progestins is associated with increased risk of mammary tumors in dogs. Female dogs that have undergone ovariohysterectomy (OHE) prior to their first estrus and male dogs have a very low incidence of mammary tumors.
Sexually intact female dogs have a relatively high overall risk of mammary tumors. According to some cancer registries, 50%–70% of all tumors in this subpopulation of dogs are mammary in origin (5, 6, 7).
The benefit of mammary tumor prevention associated with later OHE has been questioned. The original retrospective case-control study concluded that OHE after the third estrus cycle did not confer a decreased mammary tumor risk (8). However, two separate prospective studies, one of which was randomized, showed a significantly decreased risk for new tumors in older sexually intact dogs that were spayed concurrent with surgical removal of both benign (36% vs 64%) and malignant tumors (31.5% vs 58.6%) (9, 10)]. These publications confirm that the cumulative exposure to ovarian hormones after the initial first few cycles contributes to mammary tumorigenesis.
Exposure to exogenous estrogens or progestins also increases risk of tumor development (11, 12, 13, 14).
Several other factors are also associated with mammary tumor risk. Specifically, mammary tumors are rarely diagnosed before age 5; however, the risk increases gradually thereafter and the average age of dogs with tumors is 7–11 years old (15). Furthermore, purebred dogs and smaller-breed dogs, as well as consumption of a red meat diet and obesity, are also associated with increased risk (16).
Clinical Signs of Mammary Tumors in Dogs
Dogs have 4–5 pairs of mammary glands, and multiple tumors involving more than one gland and both mammary chains are very common (50%–70% of cases) (17, 18). The caudal glands are affected more often than the cranial glands.
The tumors palpate as discrete nodules or masses around the nipples and can range in size from barely palpable to large masses extending across several glands. The skin may be involved and ulcerated.
Depending on the duration of tumor growth and tumor size and type, the draining lymph nodes (ie, axillary and superficial inguinal lymph nodes) may be palpably enlarged.
Most dogs have their disease confined to their mammary chains with or without the lymph nodes and are systemically healthy when diagnosed. However, dogs with advanced metastatic disease or inflammatory carcinomas may show systemic clinical signs, such as fatigue, malaise, weight loss, and inappetence.
Diagnosis of Mammary Tumors in Dogs
Mammary tumors in dogs are usually detected on physical examination.
Cytological evaluation of a fine-needle aspirate may help rule out certain nonmammary tumor types but may not differentiate benign from malignant tumors and may not be representative of the whole mass due to the heterogeneous nature of mammary tumors. All mammary tumors should be regarded as potentially malignant. Histological evaluation is the cornerstone of diagnosis, allowing histopathological classification and grading.
Due to the risk of metastasis, which may impact treatment decisions, clinical staging is recommended before initiating treatment.
Clinical Staging
The TNM system for classification of malignant tumors (where T describes size of the primary tumor, N describes regional lymph node involvement, and M describes distant metastasis) is widely used for staging mammary carcinomas in human female patients. A modified TNM staging system is used to stage mammary tumors in dogs (19, 20). In brief, the stage advances as the size of the primary tumor increases from < 3 cm (stage I), to 3–5 cm (stage II), to > 5 cm (stage III). Regardless of tumor size, lymph node involvement represents stage IV disease and distant metastasis constitutes stage V disease (see the table Modified TNM Staging System for Canine Mammary Tumors).
Assigning a formal stage is useful for consistency in communication and for research purposes. At the clinical level, staging of mammary tumors in dogs should follow a practical approach. The purpose of clinical staging is to determine the extent of disease and overall health.
The mammary glands need to be palpated carefully, and all tumors should be identified and measured. The risk of malignancy increases with progressive tumor size (17).
Fine needle aspirates (FNAs) of the draining lymph nodes if palpably enlarged are important, so that surgical resection is planned to include any affected lymph nodes. Most tumors occur in the caudal glands and drain to the superficial inguinal lymph nodes, which typically are included if a caudal simple or regional mastectomy is planned; therefore, FNAs may be omitted in these cases.
In addition, 3-view thoracic radiographs should be performed to assess for distant metastasis.
Abdominal ultrasonography may not be needed as part of the routine presurgical staging, unless indicated by clinical signs in an individual patient. Postsurgical staging, specifically axillary and internal iliac lymph node ultrasonography, may be indicated in dogs with high-grade or aggressive histological subtypes to optimize the treatment plan and treatment-response monitoring.
Lastly, the overall health of the patient should be evaluated through a clinical examination, blood work, and urinalysis.
Histological Grading
Considering that most affected dogs have multiple mammary tumors, which may include multiple histopathological types, all tumors should be excised and submitted for histological evaluation. Several systems for histological grading of canine mammary tumors exist, using specific histopathological criteria (tubule formation, nuclear pleomorphism, and mitotic activity). Generally, tumors are graded as follows: well-differentiated (grade 1), moderately differentiated (grade 2), and poorly differentiated (grade 3).
Treatment of Mammary Tumors in Dogs
In addition to providing tissues for histopathological diagnosis, complete surgical excision achieves locoregional control in dogs with mammary tumors.
The surgical approach depends on the size and location of the tumors and may be achieved through lumpectomy, simple mastectomy, regional mastectomy, radical mastectomy, or a combination of these approaches. In dogs with multiple tumors, especially if they are spayed concurrently with tumor removal, there is no proven benefit to removing normal unaffected glands as part of a prophylactic approach (16, 21, 22).
After surgical resection and biopsy, the need for further treatment can be determined. Dogs with low-risk tumors have a low risk of developing distant metastasis and typically do not require systemic treatment (2).
In order to differentiate between low- and high-risk cases, prognostic factors can be useful. These factors include TNM stage, tumor grade, tumor subtypes, and presence of vascular invasion (1, 16, 20, 22, 23, 24, 25).
These factors can be used individually or in combination by implementing a published prognostic bioscoring system that provides improved prognostication in the individual patient (2). The development of distant metastasis is generally associated with a fatal outcome, and in theory, identifying cases at risk of metastasis and initiating effective adjuvant systemic treatment may improve outcome.
Systemic Treatment of Mammary Tumors in Dogs
Given that mammary tumors in dogs are considered hormone-dependent tumors, ovarian hormonal ablation as achieved through OHE appears to be a logical adjuvant in these cases. OHE is often performed concurrently with tumor removal and has been shown to both decrease the incidence of new tumors (independent of the type of primary tumors) and decrease or delay the incidence of distant metastasis in a subset of cases (9, 10).
Notably, this benefit is limited to dogs with estrogen-positive tumors. Tumor receptor analysis (estrogen receptor [ER] immunohistochemistry) can be helpful to identify these patients. It is, however, important that the laboratory uses an ER assay shown to predict response to ovarian hormonal ablation (10).
Chemotherapy with or without NSAIDs is often used as an adjuvant in dogs considered to be at high risk of metastasis or as a palliative for dogs with established metastasis. Many of the drugs and protocols are extracted from publications on breast cancer in humans. The data regarding effectiveness in dogs are weak (16). The studies, however, are often underpowered, retrospective, nonrandomized trials and not conducted according to evidence-based medical standards.
Nevertheless, oncologists continue to recommend and provide chemotherapy to dogs they consider to be at high risk of failing due to metastatic disease because a negative, underpowered publication may not reflect the true activity of these protocols. Further research to identify effective drugs and protocols in dogs with high-risk mammary tumors is clearly needed (16).
Prevention of Mammary Tumors in Dogs
Mammary tumors in dogs can be prevented through early ovariohysterectomy.
However, OHE at an early age may increase the risk of several negative health effects. The increased risk of hemangiosarcoma, osteosarcoma, and lymphoma is the most consequential (10, 26, 27, 28, 29). In contrast to mammary tumors, these malignancies are often diagnosed at more advanced stages, and most affected dogs will succumb to their cancer despite treatment. Because of this, the recommendations regarding early OHE must be more nuanced (see link to Hart et al article in For More Information).
Owners of breeds at risk for these aggressive malignancies are often advised to delay OHE. If OHE is delayed, however, it is important that the owners monitor their dog for mammary tumors by performing regular examinations at home. In contrast to the above highly aggressive malignancies, early detection and treatment are possible and often associated with favorable outcomes.
Key Points
Mammary tumors are the most common tumor type in female dogs.
Surgical excision of all tumors provides for histopathological diagnosis and locoregional control.
Early spaying may mitigate the risk of mammary tumors in dogs, but this is not the sole consideration in timing of spaying.
For More Information
Hart BL, Hart LA, Thigpen AP, Willits NH. Assisting decision-making on age of neutering for 35 breeds of dogs: associated joint disorders, cancers, and urinary incontinence. Front Vet Sci. 2020;7:388. doi:10.3389/fvets.2020.00388
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