10/1/2020 Mammary Carcinoma - VetFolio

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Mar 8, 2019

Mammary Carcinoma

Oncology

Sandra Axiak-Bechtel, DVM, DACVIM (Oncology)

College of Veterinary Medicine
University of Missouri, Columbia, MO

PROCEEDINGS:
NAVC Conference 2013 Small Animal

CANINE MAMMARY TUMORS

Mammary tumors usually occur in older female dogs, with an average age of 10 to 11 years. The
development of mammary tumors is hormone dependent, and time of ovariohysterectomy (OHE) is
correlated with the incidence of mammary tumors. Dogs spayed prior to the rst estrus have the
lowest risk of tumor development at 0.05%, which increases to 8% if OHE is performed after the rst
estrus and rises to 26% if OHE is performed after the second estrus.1

About half of canine mammary tumors are benign and half are malignant. Of the malignant tumors,
roughly half will metastasize. Therefore, to determine the best course of treatment, detailed
histopathology and multiple prognostic factors are used.

Diagnosis

Upon discovering a subcutaneous mass in the mammary chain, ne needle aspiration and cytology
should be pursued. Although cytology cannot always distinguish between benign tumors and
malignant but well differentiated carcinomas, this tool can rule out non-mammary gland malignancy,
which will change the approach for disease control. For example, subcutaneous mast cell tumors can
occur in the mammary region, and an enlarged super cial inguinal lymph node can represent
lymphoma. If a malignant tumor is suspected or con rmed, staging should be performed and includes
investigation of common metastatic sites, namely, regional lymph nodes, lung parenchyma, and
abdominal lymph nodes. Other less common metastatic sites are bone, liver, kidneys, adrenal glands,

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spleen, pancreas, and diaphragm. Chest radiographs, abdominal ultrasound, and lymph node
aspiration and cytology are the rst steps in staging a malignant or suspected malignant mammary
tumor.

The World Health Organization (WHO) modi ed staging system is used for canine mammary tumors.
Stage I represents a tumor less than 3 cm in size, with no lymph node or distant metastasis. Stage II is
a tumor that is 3 to 5 cm maximum, with no lymph node or distant metastasis. Stage III is a tumor > 3
cm in size, with no lymph node or distant metastasis. Stage IV is any tumor size with lymph
metastasis, and stage V is any tumor with distant metastasis, +/− lymph node metastasis.2

Prognostic Indicators

Dogs with tumors of less than 3 cm in size, especially those that are well circumscribed, have a better
outcome than dogs with tumors larger than 3 cm or those with invasive or ulcerated masses.
Histopathologic type and subtype are also important. Most canine mammary tumors are carcinomas;
while sarcomas do occur, they are much less common. The histologic subtypes of well-differentiated,
complex, or tubular/ papillary carcinoma have a better prognosis then poorly differentiated, simple,
solid, anaplastic or in ammatory carcinomas; mammary sarcomas are also a poor prognostic indicator.
In addition, tumor grade, including indices of proliferation and evidence of lymphatic or vascular
invasion can provide valuable information for treatment decisions. Evidence of lymph node
involvement or distant metastasis is also predictive of outcome.3

Treatment

Surgery is the initial treatment of choice for canine mammary tumors, with the exception of dogs with
in ammatory mammary carcinoma or distant metastasis. The primary goal of surgery in the treatment
of canine malignant mammary tumors is to use the simplest procedure to remove the entire tumor.
For example, lumpectomy is indicated for masses that are known to be benign and are super cial, not
xed, and < 0.5 cm in diameter. A mammectomy is used for masses that are >1 cm and are centrally
located within the gland. Depending on individual anatomy, however, a regional mastectomy may be a
simpler procedure. Major lymphatic connections exist between glands 1 and 2, and glands 4 and 5.
Glands 1, 2, and 3 drain to the axillary and cranial sternal lymph nodes and glands 3, 4, and 5 to the
super cial inguinal lymph nodes. Surgically, glands 1, 2, and 3 or 4 and 5 can be removed en bloc with
extensive mammary chain involvement. Radical unilateral or bilateral staged mastectomy is reserved
for those tumors in which complete removal is not achievable with a less invasive procedure. If
enlarged, axillary and/or inguinal lymph nodes should also be excised and submitted for
histopathology.1,3

Chemotherapy

Chemotherapy, although not well studied, is used for dogs with mammary tumors that have a high risk
of metastasis. This includes mammary sarcomas, mammary carcinomas of the subtypes anaplastic,
simple, poorly differentiated, or solid), those with lymphatic or vascular invasion, high grade, and
those with lymph node metastasis present. Cyclophosphamide and 5- uorouracil (5-FU) was used
successfully in a small number of dogs with Stage III disease, and prognosis was improved with the use
of this treatment regime.4 Doxorubicin and carboplatin have also studied in cell culture with ef cacy
against canine mammary carcinoma; there is a report of ef cacy using doxorubicin in two dogs with
distant metastasis of mammary adenocarcinoma.5

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Prognosis

Poorly differentiated carcinomas treated with surgery alone have reported median survival times of 2.5
months, compared with 21 months in dogs with adenocarcinoma, and 16 months in dogs with solid
carcinoma. In ammatory carcinomas have a very poor prognosis; most are rapidly progressive and
become too large and in ltrative for surgical excision. In addition, many of these dogs are systemically
ill and disseminated intravascular coagulation is frequent (reported in 21% of dogs). Tumor size is also
important; even with invasive tumors dogs with a mass of <3 cm have a better prognosis than dogs
with masses of >3 cm.2 Dogs diagnosed with mammary sarcoma have an overall poor prognosis; most
will die or be euthanized due to disease progression within 9–12 months of diagnosis. Chemotherapy
should be considered following surgery in those dogs determined to have a high risk of metastasis.

Conclusion

Factors that help predict prognosis include tumor size, histologic type and subtype, metastasis (lymph
node or distant), tumor grade, degree of nuclear differentiation, degree of invasion, and lymphatic or
vascular invasion. Surgery is the treatment of choice for canine mammary tumors, and the surgical
procedure should be the simplest procedure that can be performed to achieve complete tumor
margins. In high risk tumors, chemotherapy is recommended following surgery; 5-FU and
cyclophosphamide, carboplatin, or doxorubicin are those most commonly recommended.

FELINE MAMMARY TUMORS

In contrast to canine mammary cancer, over 90% of feline mammary tumors are considered to be
malignant. Mammary cancer is locally aggressive in cats, and due to extensive communication in
vasculature between feline mammary glands, multiple gland involvement is common. Metastasis
occurs through both the lymphatic and vascular routes, so common metastatic sites are lymph nodes,
lungs, liver, and pleura, in addition to less common sites such as bone, kidneys, and adrenal glands.
The Siamese breed may be at an increased risk of developing mammary carcinoma. As in the dog, early
OHE (prior to 1 year of age) will reduce the risk of development of mammary carcinoma by 86%. 6

Although only representing 10–20% of feline mammary tumors, benign lesions are a differential for a
mammary mass. Benign lesions include duct papillomas, simple or complex adenomas, and
broadenomas. Fibroadenomatous hyperplasia is an exaggerated proliferation of mammary tissue and
is likely hormone dependent. This condition may develop during puberty, in pregnant or
pseudopregnant queens, or in cats on hormonal therapy (megestrol acetate or maderoxyprogesterone
acetate). Treatment of choice is removal of hormone source, usually OHE performed by a ank
approach. Antiprogestins have also been used in cases where OHE is not desirable.2,6

>Malignant tumors are much more common than benign mammary tumors in cats, and carcinoma is
the most frequent type diagnosed. Common subtypes of mammary carcinoma are tubular, papillary,
ductular, anaplastic, and solid. Histologic type of carcinoma is prognostic, in that cats with papillary or
tubular mammary carcinomas have much longer survival times than ductular carcinomas, and
anaplastic carcinomas are considered to have the worst prognosis. Additionally, tumor size is
important in determining prognosis. Cats with a mass of less than 2 cm or 2–3cm in size (WHO stages I
and II respesctively) tend to have a better prognosis with surgery alone compared to cats with a mass
of > 3cm. Other prognostic factors include extent of surgery, presence and location of metastasis, and
expression of proteins including VEGF, HER2/neu, AgNOR, PCNA, COX-2, and Ki-67.

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Diagnosis and Staging

On physical examination, a discrete, palpable, and sometimes moveable mass or masses are palpated
in the mammary gland. If advanced, ulceration, erythema, and edema may be present. Fine needle
aspiration and cytology will rule out other malignancies and may potentially provide a diagnosis.

Staging in cats should be performed prior to surgery when a malignancy is suspected or con rmed due
to the high and often rapid rates of metastasis. Staging should include thoracic radiographs and
abdominal ultrasound, with ne needle aspiration of any suspicious lesions on ultrasound. In addition,
aspiration of enlarged axillary, inguinal, or abdominal lymph nodes should be performed.

Treatment

Surgery remains the rst step in treatment of feline mammary cancer. Cats have four pairs of
mammary glands, two cranial that drain to the axillary lymph node and two caudal that drain to the
super cial inguinal lymph node. There also exist small veins in all mammary glands that cross midline,
which may allow spread of malignant tumors between pairs of mammary glands. Therefore,
aggressive surgery is aimed at getting wide and complete margins. Most often, radical unilateral
mastectomy is recommended, and, in some cases, staged bilateral mastectomy. These aggressive
surgical procedures have been shown to increase disease free intervals compared to less aggressive
surgeries.2,6

Chemotherapy is used postoperatively in cats with malignant tumors with the goal of extending
disease free intervals and overall survival times. Although this survival bene t is not yet proven, due to
the inherent high metastatic rate, chemotherapy is recommended as an adjunct to surgery in most
cats. Doxorubicin-based chemotherapy protocols are among the most commonly studied and used:
single-agent doxorubicin for ve treatments or doxorubicin and cyclophosphamide combinations.7,8 In
addition, single-agent mitoxantrone compared with single-agent doxorubicin (every 3 weeks, four
treatments) has also been studied following unilateral or bilateral mastectomy, and similar median
survival times of 1.2 years were reported in both groups.9

Chemotherapy has also been used in situations where aggressive surgery is not possible. Using a
combination of doxorubicin and cyclophosphamide, a 50% partial response rate was noted in 14 cats
with mammary carcinoma in one study and 45% in another.10 Therefore, chemotherapy may be useful
in cases where surgery is not feasible, and a decrease in tumor volume may help preserve the cat’s
quality of life.

Prognosis

Overall, prognosis for cats diagnosed with mammary carcinoma is dependent on tumor size, grade,
and histopathologic subtype. When treated with aggressive surgery followed by doxorubicin
chemotherapy, cats with stage I and II mammary carcinoma have median survival times of 1.2 years
and cats with a tumor of >3 cm, 6 months. Presence of metastatic disease is a negative prognostic
indicator, although regional lymph node excision allows a decrease in bulky disease.

Conclusion

Over 80% to 90% of feline mammary masses are malignant carcinomas, and diagnostic steps should
include cytology, thoracic radiographs, abdominal ultrasound, and regional lymph node sampling to
determine if metastasis has already taken place. Aggressive surgery with unilateral or staged bilateral

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radical mastectomy is recommended for local disease control, and chemotherapy should be
considered following surgery due to the high potential for metastasis to occur.

REFERENCE:

1.

Sorenmo KU, Shofer FS, Goldschmidt MH. Effect of spaying and timing of spaying on survival of dogs
with mammary carcinoma. J Vet Intern Med. 2000; 14:266–270

2.

Lana SE, Rutteman GR, Withrow SJ. Tumors of the mammary gland. In Withrow SJ, Vail DM (eds): Small
Animal Clinical Oncology, 4th ed. 2007, pp 619–636.

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Chang SC, Chang CC, Chang TJ, Wong ML. Prognostic factors associated with survival two years after
surgery in dogs with malignant mammary tumors: 79 cases (1998–2002). JAVMA. 2005; 227(10):1625–
1629.

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Karayannopoulou M, Kaldrymidou E, Constatinidis TC et al. Adjuvant post-operative chemotherapy in

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Hahn KA, Richardson RC, Knapp DW. Canine malignant mammary neoplasia: biological behavior,
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Gimenez F, Hecht S, Craig LE, et al. Optimizing the management of feline mammary masses. J Feline
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Novosad CA, Bergman PJ, O’Brien MG, et al. Retrospective evaluation of adjunctive doxorubicin for the
treatment of feline mammary gland adenocarcinoma: 67 cases. J Am Anim Hosp Assoc. 2006;42:10–
120.

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McNeill CJ, Sorenmo KU, Shofer FS, et al. Evaluation of adjucant doxorubicin based chemotherapy for
the treatment of feline mammary carcinoma. J Vet Intern Med. 2009;23:123–129.

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Henry CJ, Higginbotham ML, Fox LE, et al. Prospective evaluation of doxorubicin vs mitoxantrone for
adjuvant therapy of feline mammary carcinoma. Proceedings of the VCS 26th Annual Meeting, 2006, p
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Mauldin GN, Matus RE, Patnaik AK, et al. Ef cacy and toxicity of doxorubicin and cyclophosphamide
used in the treatment of selected malignant tumors in 23 cats. J Vet Intern Med. 1988;2:60–65.

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