Symposium on Clinical Veterinary Oncology

Feline Mammary Tumors

Audrey A. Hayes, V.M. D. *

and Samantha Mooney, B.A., M.A. t

Mammary gland tumors are the third most common cancer in cats
after skin tumors and lymphosarcoma. 4 Although most feline mammary
gland tumors are malignant, early detection, aggressive surgical therapy,
and frequent postsurgical follow-up examinations have a significant effect
upon prolonged survival time.
This article will review the incidence, etiology, and biologic behavior
of feline mammary tumors as well as methods of treating them.

INCIDENCE

Mammary gland tumors account for 12 per cent of all malignant tumors
in cats and 17 per cent of all neoplasms in female cats. 4 The annual
incidence of feline mammary tumors reported in a survey conducted in
Alameda County, California, was 12.8 per 100,000 cats and 25.4 per 100,000
female cats in the population at risk. 5 In a survey of necropsy records for a
10-year period at The Animal Medical Center in New York City, mammary
gland tumors accounted for 10.3 per cent of all feline nonhematopoietic
tumors. 21
Mammary gland tumors are most often reported in the domestic short-
haired and Siamese breeds. Although these two breeds are probably the
most common breeds in the cat population, Siamese cats have a significantly
increased risk of developing malignant mammary gland tumors. Tumor
development also occurs at a younger age in this breed. 12
Mammary gland tumors have been reported in cats between the ages
of 9 months and 19 years. 26 At The Donaldson-Atwood Cancer Clinic of
The Animal Medical Center, the average age of 116 treated cats with
malignant mammary tumors was 10.7 years. Mammary gland tumors are

*Diplomate, American College of Veterinary Internal Medicine; Staff, The Donald son-Atwood
Cancer Clinic, The Animal Medical Center, New York, New York
tResearch Associate, The Donaldson-Atwood Cancer Clinic, The Animal Medical Center,
New York, New York

Veterinary Clinics of North America: Small Animal Practice- Vol. 15, No. 3, May 1985 513
514 AUDREY A. HAYES AND SAMANTHA MOONEY

most common in middle-aged cats, with an increased incidence rate in the

10 to 14 year age group. 18 Although Siamese cats develop mammary gland
cancer at a younger age, they experience no significant increase in incidence
after the 7- to 9-year risk plateau. 12
In Alameda County, California, the annual incidence of mammary
tumors among 100,000 female cats in the population at risk was reported
to be much higher in intact female cats (31.8) than in ovariohysterectomized
cats (20.4). Thus, intact female cats have an approximately sevenfold
increased risk of developing mammary cancer than spayed females. 5
In a review of the ovariohysterectomy status among female cats in The
Animal Medical Center hospital population and cats with mammary neo-
plasia, it was found that 60 per cent of the female cats in the general
population had been spayed. However, only 41 per cent of the female cats
with mammary neoplasms had been spayed prior to tumor development.
Seventeen per cent of the spayed cats had been ovariohysterectomized
before they were 1 year old. Thus, ovariohysterectomy at 8 to 11 months
of age did not eliminate the development of mammary cancer.

ETIOLOGY

The cause of mammary cancer in the cat is being investigated, and

recent studies indicate that the hormonal influence is etiologically signifi-
cant. Although C-type viral particles have been identified in neoplastic
feline mammary tissue, the significance of these particles has not been
determined. 7 • 24 These viral particles may be passenger viruses and not the
cause of mammary tumors in the cat.
The influence of hormones on the development of feline mammary
cancer has been a matter of dispute. Mammary tumors are epithelial in
origin and were reported to be independent of hormonal stimulation, 19
occuring in female cats who were spayed during their first year of life26 and
occuring, although rarely, in castrated and intact male cats. 15• 21• 24· 26
However, more recent findings indicate that hormonal factors may be
involved in the development of feline mammary cancer. Among seven
intact female cats who received semiannual injections of reposital proges-
terone, one cat developed mammary hyperplasia and three cats developed
mammary adenocarcinoma. 2 • 13 At The Donaldson-Atwood Cancer Clinic,
39 female cats (34 ovariohysterectomized, 5 intact) were given oral proges-
tins for the treatment of refractory eosinophilic granuloma. Six of the 39
cats (15 per cent) developed pathology in the mammary glands. Three
developed mammary hyperplasia, one developed mammary adenomas, one
developed carcinoma in situ, and one developed adenocarcinoma. Endog-
enous progesterone or the administration of progestins, 14 therefore, appears
to influence mammary hyperplasia and the development of malignant
mammary tumors.
Although estrogen receptors have not been found on feline mammary
tumor tissue, progesterone receptors and possible corticosteroid receptors
have been identified on the cell surfaces of hypertrophied feline mammary
gland tissue 10 and tumor tissue.6
fELINE MAMMARY TUMORS 515
Cats are seasonally polyestrous, and it is possible for female cats to
have their first estrous cycle as early as 5 months of age. Therefore, in an
effort to prevent mammary tumor development, cats not intended for
breeding should perhaps be ovariohysterectomized prior to their first estrus
or prior to 6 months of age. In the United States, elective ovariohysterec-
tomy is usually performed on cats 8 to 10 months of age. Consequently,
there are no data concerning the effects of earlier ovariohysterectomy in
preventing feline mammary tumors. There is no evidence that ovariohys-
terectomy at the time of mastectomy prevents tumor recurrence or prolongs
survival time. 1' 19

BIOLOGIC BEHAVIOR AND TUMOR MORPHOLOGY

All mammary glands in the cat are equally susceptible to tumor

development. 2 At The Donaldson-Atwood Cancer Clinic, 60 per cent of the
116 cats presented with mammary tumors had multiple gland involvement.
In one third of these cats, both right and left mammary gland chains were
simultaneously involved.
The histology of a total of 264 feline mammary tumors has been
described. 2• 3• 9 · u. 19 · 22 • 26· 27 Of these tumors, 227 (86 per cent) were malig-
nant and 37 (14 per cent) were benign. Tubular and papillary adenocarci-
nomas were the most common histologic type of mammary tumor, followed
by solid carcinomas. A few mammary sarcomas have been reported. 20 • 26
Feline mammary tumors have two distinct histologic features. They contain
extensive areas of necrosis, and there is often lymphocyte and plasma cell
infiltration. 19• 26 There appears to be no correlation, however, between the
degree of lymphocyte and plasma cell infiltration and survival time. 26
A histologic grading system for feline mammary tumors has been
established based on the following factors: (1) cellular differentiation and
the degree of tubule formation; (2) nuclear pleomorphism; and (3) mitotic
frequency. Cats with well-differentiated tumors with low pleomorphism
and few mitotic figures appear to have an increased survival time. 26
Feline malignant mammary tumors grow rapidly and metastasize to
regional lymph nodes and lungs. 2• 3• u. 19• 26 The tumors usually occur in the
subcutaneous tissue adjacent to the nipple and adhere to the overlying
skin. Tumor progression is often accompanied by cutaneous ulceration and
invasion of the underlying musculature. 19
In 25 per cent of the cats with mammary tumors, tumor cells are
observed within the lymphatic system that drains the involved glands
regardless of the histologic type. Less frequently, tumor cells ar'e also found
within blood vessels. 20
In one study of mammary tumors in 60 cats, a statistically significant
inverse relationship (p less than 0.01) was found between tumor volume
and the likelihood of a cat surviving 1 year. 26 At The Donaldson-Atwood
Cancer Clinic, in a study of 91 cats with malignant mammary tumors,
tumor volume was found to be the most important factor affecting prognosis
after surgery. Eighteen cats with a tumor volume of 28 cc or greater had
a median survival time of 6 months. Nineteen cats with a tumor volume of
 516 AUDREY A. HAYES AND SAMANTHA MOONEY

9 to 27 cc had a median survival time of 2 years. Fifty-four cats with tumor

volumes less than 8 cc had a median survival time of 4.5 years. 16 These
findings emphasize the importance of early detection and diagnosis and the
need for immediate therapy.

THERAPY

Although surgery is the most common treatment for feline mammary

tumors, follow-up studies of mastectomy patients reveal a high incidence
of recurrence and metastasis. 2 A World Health Organization study reported
that only 15 of 170 cats with malignant mammary tumors were alive 1 year
after surgery. 76 Other studies have reported postoperative survival as rarely
more than 6 months. 8• 25 The high malignancy rate among feline mammary
tumors and the variation in surgical procedures are thought to account for
the high incidence of tumor recurrence and metastasis reported.
The spread of tumor cells occurs by direct growth along lymphatic
channels or by the presence of tumor emboli located in the venous drainage
from the mammary glands. Small veins that cross the midline could lead
to the appearance of malignant eels in a pair of glands. 19 In a study of
mammary gland lymphatic drainage in normal cats, it was found that the
pectoral glands on each side drain into one another and into the axillary
lymph nodes. The abdominal glands also drain into each other and into the
superficial inguinal lymph node. The lymphatic vessels do not penetrate
the thoracic or abdominal wall and rarely cross the midline or the area
between the pectoral and abdominal glands. Thus, a malignant tumor in
· the pectoral gland necessitates the surgical removal of both pectoral glands
and the axillary lymph node on that side. Similarly, surgery for a tumor in
the abdominal gland involves removal of both glands and the superficial
inguinal lymph nodes. 28
In order to improve the effectiveness of surgery in the treatment of
feline mammary tumors, aggressive, standardized surgical protocols should
be followed . In a study comparing conservative and radical surgery in 91
cats, The Donaldson-Atwood Cancer Clinic found that the type of surgery
was significantly (p less than 0.01) related to time of disease-free interval.
Cats treated with radical mastectomy had a longer disease-free interval (575
days) than cats treated with conservative surgery (325 days). A similar but
nonsignificant trend was noted for survival time (800 versus 500 days). 16
The protocol used by The Cancer Clinic is outlined in the following
paragraphs.
All cats with primary mammary tumors with no radiographic evidence
of metastatic disease and with no other diseases should undergo radical
mastectomies. A radical mastectomy is defined as the removal of all four
glands of the affected mammary chain plus the ipsilateral axillary and
inguinal lymph nodes. If tumors are present in both mammary chains, two
radical mastectomies are performed. The chain of glands with the larger
·tumor volume is usually removed first. The second mastectomy is done a
month later.
This surgical protocol is threefold in purpose. In its aggressive ap-
fELINE MAMMARY TUMORS 517

proach, it renders affected cats free of disease as quickly as possible. Large

amounts of mammary tissue are removed, with little mammary tissue
remaining along the affected chain of glands, which decreases the chance
of recurrence. Lastly, this protocol is a standard surgical approach for the
treatment of cats with mammary tumors. Standardization of the surgical
approach to mastectomy eliminates one important and undesirable variable
in the evaluation of the effectiveness of therapy for cats with malignant
mammary tumors. It also makes possible cooperative studies between
veterinary institutions and private practitioners.
There are four other classes of cancer therapy that can be used in
conjunction with surgery: (1) radiation; (2) chemotherapy; (3) hormonal
therapy; and (4) immunotherapy. There are no published reports concerning
the effectiveness of radiation, chemotherapy, or hormonal therapy in cats. 28
The postoperative use of cyclophosphamide has been reported in cats with
highly malignant mammary tumors, although no results are available at this
time. 23 At The Donaldson-Atwood Cancer Clinic, low-dose chemotherapy
using vincristine, cyclophosphamide, and methotrexate was found to be
ineffective in the prevention of recurrence or metastasis. A protocol using
adriamycin and cyclophosphamide is presently being evaluated for cats with
metastatic and/or unresectable mammary gland neoplasia.
Antiestrogen drugs are not indicated in the treatment of feline mam-
mary cancer owing to the absence of estrogen receptors on tumor tissues
in cats. The potential role of hormonal therapy in the treatment of feline
mammary tumors is dependent upon an increased understanding of the
hormonal influence on mammary tumor development.
Immunotherapy is an attempt to initiate or augment an immunologic
-reaction to disease. The rationale for immunotherapy is that tumor-specific
antigens exist and that the immune response to these antigens can be
enhanced by immunoadjuvants. Although tumor-specific antigens have not
been found to be associated with feline mammary carcinomas, these antigens
exist in many animal tumors. Immunologic reactions occurring in response
to these antigens can influence the course of malignant disease. 28 Adjuvant
immunotherapy may prove useful in preve nting tumor recurrence and
extending the survival time for cats with mammary cancer.
The Donaldson-Atwood Cancer Clinic is continuing to compare the
effectiveness of immunotherapy combined with surgery to the effectiveness
of surgery alone in the prevention of recurrent disease and extension of
patient survival time. Our original study of 51 cats revealed a median
survival time of 450 days for cats treated with surgery alone as compared
to a median survival time of 875 days for cats treated with surgery and a
microbial immunoadjuvant (MBV). * The results of this nonrandomized
study were not found to be statistically significant.
In a recent double-blind clinical trial at The Donaldson-Atwood Cancer
Clinic, 64 cats were randomized into a treatment group receiving radical
surgery alone or a group receiving surgery plus a chemical immunoadjuvant

*Mixed Bacterial Vaccine (S treptococcus pyogenes and Serratia marcescens). Farben

Fabriken, Bayertal, Germany.
518 AUDREY A. HAYES AND SAMANTHA MOONEY

(levamisole). * No significant differences were found in recurrence or

survival times.

POST-THERAPY FOLLOW-UP

Studies indicate that most cats with mammary tumors that are treated
by surgery eventually die of recurrent and/or metastatic disease. 2 At The
Donaldson-Atwood Cancer Clinic, disease recurred in 76 (66 per cent) of
116 treated cats in a median time of 5.5 months. Reported survival times
vary and have been shown to be dependent upon several factors. To review,
the following are the most significant factors affecting recurrence and
survival times:
l. Tumor volume
2. Type of surgery
3. Histologic diagnosis and grading

Frequent examinations are an important part of the postoperative

treatment of cats with mammary tumors. The owner of a cat with mammary
cancer should be informed of the malignant nature of the disease in order
to ensure client cooperation in follow-up care. Frequent follow-up exami-
nations allow for detection of early-stage tumor recurrence. Successful
surgical resection is often difficult or impossible once recurrent disease
becomes widespread. At The Donaldson-Atwood Cancer Clinic, cats treated
with surgery alone are examined bimonthly. Each cat receives a complete
physical examination with emphasis on palpation of the previous incision
line(s), the re maining mammary glands, and the axillary and inguinal lymph
node regions in order to detect recurrent disease. Auscultation and percus-
sion of the heart and lung fields are also important. Thoracic radiographs
are taken every 3 to 6 months.

SUMMARY

The characteristics of feline mammary cancer-that is, the rapid growth

of primary mammary tumors, the high rate of tumor recurrence, and the
poor survival statistics-demonstrate the need for (1) early diagnosis of the
primary tumor; (2) immediate, aggressive surgical therapy; and (3) frequent
follow-up examinations to detect early clinical signs of recurrent disease.
A number of factors that influence prognosis have been described. As
more information becomes available concerning the behavior of feline
mammary tumors and the results of various forms of treatment, more
effective protocols can be developed. Continued etiologic research may
play a vital role in determining the direction of therapy.

*Levamisole Hydrochloride. Pitman-Moore, Inc., Washington Crossing, New Jersey.

FELINE MAMMARY TUMORS 519

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The Donaldson-Atwood Cancer Clinic

The Animal Medical Center
510 East 62nd Street
New York, New York 10021