Mammary Cancer
Bladder, Brain, Head & Neck, Hemangiosarcoma, Lymphoma, Mammary, Mast Cell Tumor, Osteosarcoma, Skin, Testicular Cancers
Antiangiogenesis, Chemotherapy, Clinical Trials, Radiation, Surgery, Complementary & Alternative Treatments
Afterlife
Definition
Symptoms
Risk Factors
The development of benign mammary tumors, not malignant tumors, has been linked to the female reproductive
hormone, progesterone. Despite this, however, spaying a female prior to 2-1/2 years significantly decreases risk for both
benign and malignant mammary tumors. Spaying after this time reduces risk for benign tumors but appears to have no
advantage for prevention of malignant tumors. These results would indicate that hormones do not have a direct
mutagenic effect on mammary cells. Rather, it is believed that hormones, through their promotion of cellular growth,
increase the number of cells that may be susceptible to malignant transformation. This is consistent with the finding that
benign growths are susceptible to becoming malignant. Early spaying may therefore, reduce occurrence of malignant
lesions because the procedure removes the source of the hormones that cause some mammary cells to lose growth
control, which puts these dividing cells at high risk for mutation and malignant transformation by environmental
carcinogens.In fact, recent reports have identified activation of a specific oncogene in a number of canine mammary
tumors. Interestingly, pregnancy and lactation appear to have no influence on mammary cancer risk, however, evidence
suggests that females bred extensively beginning at an early age have a slightly lower risk for mammary cancer.

Approximately 50% of malignant mammary tumors in the dog have receptors for either estrogen or progesterone. This
means that the presence of these female hormones promotes the growth of these tumors. Benign tumors also have
female hormone receptors and can also be stimulated by hormonal cycling of the female dog. This means that spaying is
important even if a tumor has already developed; in one study, female dogs spayed at the time of mammary tumor
removal or two years prior lived 45% longer than those who remained unspayed.
A mammary tumor is a tumor originating in the mammary gland. It is a common finding in older female dogs that are not spayed (the incidence rate is
one in 4 in unspayed female dogs over the age of 4), but they are found in other animals as well. The mammary glands in dogs are associated with
their nipples and extend from the underside of the chest to the groin on both sides of the midline. There are many differences between mammary
tumors in animals and breast cancer in humans, including tumor type, malignancy, and treatment options

Mammary tumors can be small, simple nodules or large, aggressive, metastatic growths. With early detection and prompt treatment, even some of the
more serious tumors can be successfully treated.

There are multiple types of mammary tumors in dogs. Approximately 50% of all mammary tumors in dogs are benign, and the other 50% are
malignant. The most common benign form of canine mammary tumors is actually a mixture of several different types of cells. For a single tumor to
possess more than one kind of cancerous cell is actually rare in many species. This combination cancer in the dog is called a 'benign mixed mammary
tumor' and contains glandular and connective tissue. Other benign tumors include complex adenomas, fibroadenomas, duct papillomas, and simple
adenomas.

The malignant mammary tumors include: tubular adenocarcinomas, papillary adenocarcinomas, papillary cystic adenocarcinomas, solid carcinomas,
anaplastic carcinomas, osteosarcomas, fibrosarcomas, and malignant mixed tumors.
Causes
Diagnosis
Mammary tumors present as a single lump, a solid mass or as multiple swellings in the mammary gland tissue. They are usually easy to detect by gently palpating the
mammary glands.  Benign growths are often smooth, small and slow growing. Compared to benign growths, malignant growths may grow rapidly, have irregular shape, feel
"fixed" to the skin or underlying tissue, and/or become ulcerated.  Occasionally tumors that have been small for a long period of time may suddenly grow quickly and
aggressively, but this not the usual progression.

A female dog normally has 8-10 mammary glands, each with its own nipple.  Breast cancer can and does occur in any or all of the glands, but usually occurs in the glands
located closest to the hind legs. In 50% of the cases, more than one growth is observed.

Malignant tumors may occur simultaneously with mastitis in lactating females and become apparent when symptoms of mastitis are resolved with antibiotics. Inflammatory
carcinoma, an extremely aggressive form of mammary cancer, is similar to mastitis in appearance but should be immediately suspected when its symptoms occur in a
non-lactating female. This cancer presents as a mass that may involve several or a chain of the mammary glands. The effected area appears red, swollen, and warm to the
touch. In fact, touching the area results in obvious discomfort to the female.
There are few cancers that are as easily prevented as mammary cancer in dogs. The risk of breast cancer is almost
eliminated in dogs that are spayed before their first heat.  The risk of malignant mammary tumors in dogs spayed after
their first heat increases significantly, but if an owner waits to spay their dog until after their second heat, the risk
increases to 25%.  It is believed that the elimination or reduction of certain hormonal factors causes the lowering of
incidence of the disease in dogs that have been spayed. These factors are most likely estrogen, progesterone, a similar
hormone or possibly a combination of two or more of these.

Pregnancy and lactation appear to have no influence on mammary cancer risk, however, evidence suggests that females
bred extensively beginning at an early age have a slightly lower risk for mammary cancer.

Mammary tumors are most commonly found in unspayed, middle-aged female dogs between the ages of 5 and 10 years.  
However, they can also be found in unspayed dogs as young as 2 years in rare instances. These tumors are extremely
unusual in dogs that were spayed under 2 years of age. Occasionally, mammary tumors will develop in male dogs and
these are usually very aggressive and have a poor prognosis.

Breeds at increased risk include:  poodle, Brittany spaniel, English setter, pointer, fox terrier, Boston terrier, cocker
spaniel.

Early spaying is still one of the best things pet owners can do to improve the health and ensure a long life for their dogs.
It is very difficult to determine the type of tumor based on its appearance.   A biopsy or tumor removal and analysis are almost always needed to determine if the tumor is
benign or malignant, and to identify what type it is.  A needle aspirate can be performed to help preliminarily diagnose the illness.  The procedure entails the withdrawal of
some cells through a syringe.  The cells are sent to a laboratory, which can determine whether the tumor is benign or malignant with enough accuracy to determine how
aggressive the surgical approach should be. Needle aspirate may be a helpful pre-operative procedure in many cases, but it the biopsy is ultimately what is required to
determine the extent of disease.

Tumors, which are more aggressive may metastasize and spread to the surrounding lymph nodes or to the lungs. A chest x-ray, abdominal ultrasound, and physical
inspection of the lymph nodes will often help in determining this.  Also, a compete blood cell count, chemistry profile, and urinalysis will probably be ordered to evaluate the
function of the internal organs

Dogs with benign tumors usually do not require more than the removal of the tumor as treatment,  However, cases with malignant tumors should be staged (evaluated for
metastasis). Dogs with small (less than about 1 inch diameter) low histologic grade carcinomas and adenocarcinomas with no evidence of metastasis may be treated
effectively with surgery alone. Dogs with large or invasive tumors, high histologic grade, sarcomas (tumors of mesenchymal origin), lymph node involvement and/or other sites
of spread are at risk for both recurrence of the original tumor and metastasis.

The following are common classes of mammary tumors that might be found on a biopsy.

Fibroadenoma:
A benign glandular tumor for which no treatment is necessary.

Mixed Mammary Tumor:
What is mixed is the type of cell that makes up the tumor: the epithelial cells that line the glandular tissue and the mesenchymal cells that make up the non-glandular portion.
(Mixed does not refer to a mix of benign and malignant cells.) The mixed tumor can be either benign or malignant and the biopsy will indicate this.

Adenocarcinoma:
Adenocarcinomas can be tubular or papillary, depending on the gland cells the tumor arises from. Adenocarcinomas behave malignantly but how aggressively malignant they
are depends not on whether they are tubular or papillary, but on other cellular characteristics described by the pathologist (such as how quickly the cells appear to be
dividing and how closely they resemble normal gland cells). When the oncologist reads the description he or she will be able to determine how aggressively to combat the
tumor.

Inflammatory Carcinoma:
A highly malignant tumor that generates tremendous inflammation locally with ulceration, pus, and discomfort. This type of tumor tends to spread early in its course and is
difficult to treat. Fortunately, this especially tragic tumor type accounts for less than 5% of mammary tumors.

Approximately 50% of malignant mammary tumors will have already spread by the time of surgery.  The other 50% are confined locally and surgery is curative.
Prompt surgical removal of any mammary tumor is recommended, unless the dog is very old or has other medical conditions that would rule out this option.  If a surgery is in
the early stages of this disease, the cancer can be totally eliminated in over 50% of the cases having a malignant form of cancer. The area excised depends on the judgment
of the veterinarian. Sometimes, only the mass itself will be removed. This is usually only done when the tumor is very localized.  However, because of how this cancer
spreads, it is generally advisable that radical surgery be performed which entails the removal of the mass and all the mammary tissue and lymph nodes that drain with the
gland.  With some types of tumors, especially sarcomas, complete removal can be difficult and many of these cases will have tumor regrowth at the site of the previously
removed tumor.  Radiation therapy, chemotherapy and anti-estrogen therapy alone have been used to treat inoperable mammary cancers, although not very successfully.

In advanced mammary cancers where metastasis has occurred or in which the tumor is fixed to the underlying tissues, surgery will not be curative but may be considered an
option to reduce local tumor-burden and improve quality of life.

Owners may confuse the surgical removal of a mammary gland of a dog with a radical mastectomy in humans. In humans, this type of surgery would affect the underlying
muscle tissue, which complicates the recovery. In dogs, all of the breast tissue and the related lymphatics are outside of the muscle layer, so it is necessary to only to cut
through the skin and the mammary tissue. This makes the surgery much easier and recovery much faster. A radical mastectomy in dogs means all the breasts, the skin
covering them, and the four lymph nodes are all removed at the same time. Although this is major surgery, normal activity will likely resume after the sutures have been
removed (10-14 days post surgery).

Many veterinarians will spay a dog having a mastectomy.  There is evidence that she will benefit by having the ovaries and uterus removed because it can reduce her
chances of masking her tumors with a false pregnancy and eliminates the risk of ovarian and uterine tumors.  Additionally, spaying will allow easy detection of any new tumors
that may arise because following surgery, the mammary tissue will shrink (atrophy).

In veterinary hospitals with the necessary equipment, sometimes surgery will be performed with intraoperative radiation in an effort to reduce the chances of local
recurrence.   Follow up radiation therapy to the primary site and draining lymph node may also help reduce the problem of local recurrence and local metastasis.  

The most commonly used chemotherapy protocol for the prevention of metastases from malignant breast cancer in dogs had been Adriamycin every 21 days and oral
Cytoxan every other day for 8 weeks or on day 3-6 of each 21 day cycle. However more recently,  many oncologists have switched to the use mitoxantron (Novantrone™)  as
a first choice and then Adriamycin or Carboplatin for resistant disease.   Treatment with chemotherapy may reduce the ability of the circulating cancer cells to metastasize to
the lungs.

Some veterinarians recommend supplements that are shown to reduce the risk of breast cancer for women: Inositol hexaphosphate (IP6 derived from rice), and 1-3-beta
glucan (derived  from yeast).  It can make sense to recommend these products for life since intact female dogs have the highest incidence of breast tumors than any other
companion animal and three times the incidence of breast tumors than women.  If these “Chemoprevention supplements are added to the diet, they may play a role in the
prevention of recurrent breast tumors in predisposed dogs.

Clinical studies examining the efficacy of the systemic chemotherapeutic agent Tamoxifen (a drug often given to women with breast cancer) for advanced mammary cancer in
dogs has shown no measurable therapeutic gain in any of the dogs within the study.
The type of tumor is important in determining the prognosis in dogs. Other factors include:

The size of the tumor:  tumors with diameters larger than 1.5 inches have a worse prognosis than smaller tumors.  The larger the breast tumor, the greater the risk that it has
spread to the lymph nodes, lungs, or other parts of the body.  Tumors less than 3 cm in size have a the recurrence rate is relatively low, versus greater than 3 cm has a fairly
high recurrence rate

Evidence of spread to the lymphatic system (such as the presence of tumor cells in a local lymph node or visible tumor cells with in lymphatic vessels on the biopsy) carries a
worse prognosis.

Deeper tumors or tumor adherence to deeper tissue structures carries a worse prognosis.

An ulcerated tumor surface carries a worse prognosis.

A history of especially rapid growth carries a worse prognosis.

The biopsy sample will not only identify the tumor type, it will also indicated whether or not the tumor was completely removed (so called "clean" or "dirty" margins). Tumors
removed with clean margins carry a better prognosis. If the tumor was not completely removed, a second surgery should be considered to remove more tissue.

If the biopsy report indicates that the breast tumor has spread to the lymph nodes, lymphatic channels, or blood vessels the prognosis is poor.

If the biopsy report indicates that the tumor is surrounded by cells called lymphocytes, a better prognosis is expected.   
Prognosis
Treatment
Canine Mammary Cancer Clinical Trial

The Auburn University College of Veterinary
Medicine is conducting clinical trials in
canine breast/mammary cancer to evaluate
the effectiveness of a revolutionary new cell-
based vaccine technology designed to
enhance the patient’s own immune
recognition and response to mammary
cancer. This treatment takes advantage of
the latest research into the biology of canine
cancer. We are looking for dogs for potential
recruitment in the clinical trial prior to
treatment. We encourage you to refer such
cases, with a presumptive diagnosis of
mammary cancer, for enrollment and
treatment under this protocol.
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