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Prognostic Factors for Canine and Feline Mammary Cancer

Rodney Page United States

Canine

Incidence

Second most common neoplasm in dogs. Most common malignant tumor in dogs.

162–198/100,000 dogs at risk or 260/100,000 sexually intact dogs at risk.
25–50 % of all canine neoplasms.
High-risk breeds: Poodle, English Spaniel, English Setter, Terriers.
Low-risk breeds: Boxer, Chihuahua

Etiology and Risk Factors

Hormonal Influence.
Age at ovariohysterectomy.
Body Conformation: Lean conformation at nine to twelve months correlated with reduced risk.
BRCA1 gene mutations: presently unknown but suspected in ~10% of human breast cancer.

Biologic behavior:

Location: About 65 % of the tumors occur in the caudal two glands.(4,5) Seventy-five percent are solitary.
Hormonal Receptor Status

ER (estrogen receptor) and PR (progesterone receptor) are found in canine mammary tumors.
~ 40-60% ER (+) and predicts for favorable outcome compared to ER (-).

General clinical behavior

Approximately 50–60 % of mammary neoplasms are benign.
Approximately 25 % of the malignant tumors may result in mortality.

Histopathology

Ninety percent epithelial origin:

Seventy percent adenocarcinoma (solid, tubular, papillary).
Twenty percent ductal (inter or intralobular).

Mammary tumors may have one cell type present (simple) or have ductular and secretory cells (complex) or have both elements of carcinoma and sarcoma (mixed).
Further subdivisions include:

Infiltrating or noninfiltrating.
Inflammatory: 4% of all mammary gland tumors.

Treatment

Surgery. Lumpectomy, mammectomy, regional mastectomy, unilateral or bilateral radical mastectomy. Concurrent OHE is of benefit.

Other. Chemotherapy, immunotherapy, radiotherapy, hormonal. No long-term survival benefit identified although high-risk patients should be considered for adjuvant therapy trials. Tamoxifen should be evaluated in ER (+) tumors. Inflammatory type mammary cancer associated with coagulopathy. Therefore, surgical manipulation not recommended.

Prognostic factors

Non-prognostic Factors:

  Age, breed and reproductive.

  Location or multiplicity.

  Duration of tumor.

  Type of surgery (simple, regional, radical).

Prognosis Summary

  Recurrence @ 1 yr Recurrence @ 2 yr Mortality
Size (Gilbertson, et al.,)

< 3 cm   diam

30%  40%

> 3cm  

70% 80%
Lymph node Inv (Gilbertson, et al.,)
 
90% 100%
Histologic Type (Benjamin et al.,)

Lobular (AdenoCa, Myo)

NA NA 20%

Ductular

NA NA 65%

All others

NA NA 15%
Histologic Stage—all types (Gilbertson, et al.,)

0             Locally confined (in situ)  

10% 20 %

I              Local Invasion

Well Diff

40% 40%

Moderate

40% 63%

Poor

40% 77%

II            Vascular/Lymphatic Invasion  

85% 95%

Feline                       

Incidence

Mammary gland neoplasia is the third most common form of cancer in cats. It represents approximately 10% of all non-lymphoid forms of cancer. It is more common than in humans but less common than in dogs. The average age of occurrence is approximately 10 years. Cats that are neutered have a significantly reduced risk of developing mammary cancer compared to sexually intact cats. Siamese cats are reported to be at increased risk of mammary cancer.

Etiology

The etiology is unknown although retroviral particles have been identified within breast tissue it is not associated with development. The feline BRCA1 gene has not been identified to date so the contribution of mutations to this gene to the overall incidence of breast cancer in cats is unknown. Hormonal status influences the incidence of breast cancer as mentioned above. Feline breast tissue does not routinely express high estrogen receptor levels.

Progesterone receptors are expressed at significant levels in feline mammary cancer. The reason and significance of this is unknown but it does influence treatment options (tamoxifen, an antiestrogen is not likely to be effective in cats). Cats treated with progesterone compounds such as ovaban for estrus control have a much higher rate of cancer development.

Clinical Behavior

Approximately 85% of feline mammary neoplasms are histologically malignant. Cancer may arise from either glandular or ductal tissue and tumors are categorized as either solid (35%), tubular (50%), or papillary (15%). Fifty percent of cats may have multiple glands develop tumors simultaneously. Local extension may be significant with rapid spread to regional lymph nodes and a relatively high rate of distant metastasis if not detected and treated early.

Diagnosis and Staging

Diagnosis is generally trivial with a mass arising in the glandular tissue associated with the mammary gland surrounding the nipple. Cats can develop a mammary gland hyperplasia that may resemble multiple mammary tumors but this condition generally involves multiple glands, is uniform and is hormonally responsive. Staging evaluation of a cat with mammary cancer should include survey radiographs of the chest, laboratory evaluation and any other assessments as dictated by a thorough physical exam. Staging criteria based on prognostic information is described below.

Treatment

Surgery. Radical, unilateral or staged bilateral mastectomy is the procedure often recommended due to malignant nature of most mammary tumors in cats and the likelihood of multiple tumors within different glands. Radical resection produced better local control but was not better than regional or simple mastectomy in terms of overall survival. Therefore, local or regional mastectomy may be considered if the tumor involves the most caudal or cranial glands on one side, if there are favorable prognostic factors (see below) or if follow-up therapy (chemotherapy) will be instituted. Draining lymph nodes should be excised. The axillary node may be difficult to identify but the inguinal lymph node should always be removed and submitted for histopathologic evaluation.

Chemotherapy. Adriamycin alone or Adriamycin/Cytoxan combined have been associated with significant reductions in tumor volume in the majority of cats treated. This implies the potential for pre-operative treatment of feline tumors to significantly downstage the local disease. Other chemotherapeutic compounds have not been evaluated thoroughly. Improved survival following adjuvant chemotherapy in cats with mammary cancer has also not be definitively confirmed.

Hormonal therapy. Since the majority of cats do not possess significant estrogen receptors, antiestrogenic therapy is not likely to be of value.

Radiation therapy. Little information exists to determine the effectiveness of radiation therapy for feline mammary cancer. Response of human breast cancer to irradiation, however, indicates a potential role in feline mammary cancer.

Prognosis

A large body of new evidence has been accumulated in the last three to five years indicating several new prognostic features for feline mammary cancer outcome. The known prognostic indicators are listed below.

1. Size is prognostic  

Median Survival

< 2 cm diam

36+ months

2–3 cm 

24 months

> 3 cm

6 months

2. Lymph Node involvement (ln (+) - 6 months vs. LN (-) - 18 months median survival)

3. Histologic parameters (MI (mitotic index), cell pleomorphism, tubule formation)

Category 

Prevalence 1 yr survival
    (following simple/regional resection)

Well differentiated

 (13%) 100%

Moderate

(60%) 42%

Poor

(27%) 0

4. Biologic Parameters

Proliferation status (Ki-67 ag expression).

High proliferation—12% cats survived one yr after nonradical resection.

Low proliferation—88% survived one year.

Summary

Small, well-differentiated mammary tumors without lymph node invasion should have prolonged survival after a regional or simple, but complete resection. Adjuvant chemotherapy is not indicated in this group. Larger, more poorly differentiated or high grade and invasive tumors with lymph node extension will require significant, multimodality management regimens including surgery and chemotherapy. Pre-operative chemotherapy may be of benefit for large, invasive tumors. The prognosis for the latter category remains guarded to poor.


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