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Mammary Cancer

The following information is simply informational. Its intent is not to replace the advice of a veterinarian nor to assist you in making a diagnosis of your pet. Please consult with your own veterinary physician for confirmation of any diagnosis. Your pet’s life may depend on it.

OVERVIEW

Did you know that half of all the tumors in female dogs are preventable breast tumors? Dogs develop breast cancer because they were not spayed before their first or second heat period. Intact female dogs are highly prone to developing breast tumors. In fact, they are seven times more likely to get breast cancer than a spayed dog. One out of four intact female dogs over 4 years of age will probably develop one or more breast tumors along the mammary gland chains. Half of all tumors are malignant and unfortunately, half to 75% of them will kill the dog by recurrence or spreading (metastasizing) to the lungs within one to two years. German Shepherds, Dobies and Nordic Breeds seem to do poorly, while poodles, terriers and cockers seem to have greater incidence. Sex hormones produced by canine ovaries during their six-month cycle cause a harmful sensitization or pre-programming of the breast tissue. This hormonal influence ultimately causes point mutations in the genes of the breast tissue cells that dictate tumor growth. Progesterone and estrogen are the hormones that cause this “field cancerization” effect. Progesterone therapy may cause breast tumors in dogs.

The sex hormone receptors in canine mammary tumors have not been good indicators for therapeutic response due to their very low level of activity. If the tumor has positive estrogen or progesterone receptors, it tends to be benign. An intact female dog may develop a tumor in any one of her ten mammary glands and over half will present with more than one tumor.

CLINICAL

There can be a single or several tumors, and they can occur in one or more glands. The last two sets of glands (the 4th and 5th glands) are most commonly affected. The tumors can be firm or soft, well-defined lumps or diffuse swellings. Tumors can be attached to underlying tissues or moveable, skin-covered or ulcerated. They can be different sizes, and they may grow slowly or quite fast. Most dogs are seen by the veterinarian for signs associated with the primary tumor and are otherwise feeling well. A few dogs are diagnosed with advanced metastasis (tumors that have spread to elsewhere in the body, such as the lungs and lymph nodes) and might be feeling ill from their tumors when they come for treatment.

DIAGNOSIS/INITIAL EVALUATION

Fine needle aspiration is controversial for breast tumor classification. I like to perform cytology on mammary tumors before surgery because it is wise to rule out mast cell cancer and cystic disease. I recall a case where cytology proved to be very important. Several years ago, an intact female Maltese was given a poor prognosis and turned down for breast cancer surgery by a boarded surgeon’s office. The grief stricken family came in for a second opinion. The dog had multiple firm nodules along both mammary chains. During consultation, I aspirated one nodule from every mammary gland and found cystic fluid in each with no cancer cells. Some tumors appear benign and others appear “hot” on the cytology slide. If the tumor appears in multiple glands and looks “hot” (malignant) on cytology, I recommend pre-surgical planning for a more extensive surgery such as radical mastectomy to include the draining lymph nodes. If we educate our pet owners, they’ll want to discuss the pros and cons of surgery.

STAGING

Mammary gland tumors can be either malignant (cancerous) or benign (non-cancerous) and arise from the different types of tissues (epithelial or glandular tissues, and mesenchymal or connective tissues) in the mammary gland. The most common types are tumors from the glandular tissues and include adenoma, carcinoma, and adenocarcinoma. Half of all mammary gland tumors are benign and can be treated successfully with surgery alone. The other half are malignant and have the potential for metastasis. The outcome for patients with malignant mammary gland tumors depends on several factors including tumor type, histologic grade (appearance of the tumor cells under the microscope and how similar or dissimilar they are to normal tissues), tumor size, and tumor stage (presence of regional and distant metastasis).We recommend that all mammary gland masses are surgically removed and biopsied to determine the tumor type. Dogs with benign tumors usually do not require further treatment, but cases with malignant tumors should be staged (evaluated for metastasis by tests such as chest X-rays and abdominal ultrasound). 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.

TREATMENT

There is no question that all firm breast tumors should be promptly removed and sent to the lab for biopsy. Mammary tumors should always be removed because they only get bigger. If the tumor is smaller than 3 cm in size, the dog will live longer. If the dog is not spayed, there is now proof that she will benefit by having the ovaries and uterus removed (OVH). A belated OVH for a tumor-bearing dog can reduce her chances of masking her tumors with a false pregnancy. She can also be spared the common problem of infection of the uterus (pyometra) that follows about a month after estrus. OVH also eliminates the risk of ovarian and uterine tumors. Whenever possible, I prefer a wide surgical removal over a conservative procedure. If a singular mass is presumed to be malignant, I prefer that the entire tumor is removed with a normal gland above and below the mass. Since all the breast tissue is pre programmed to make tumors, I feel that the dog may be truly better off with the susceptible mammary tissue being removed; however, the literature does not suggest this for localized tumors. If the biopsy report shows that the tumor is malignant and has invaded into the lymph system or if the surgical margins were dirty, a second surgery is suggested to get clean margins and the local draining lymph node for biopsy. In specialized centers, surgery along with intraoperative radiation may reduce or arrest a vicious cycle 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. Sheena, a beautiful brown Dobie, was presented in distress. The Figuroa family was heart broken with the news from their referring vet that Sheena could not be helped with further surgery. Sheena had two rapid recurrences at the same site and then developed an enlarged right axillary lymph node that threatened her life. We quickly started Sheena on radiation and chemotherapy. In February, 2001, Sheena celebrates her 3-year anniversary.

For the past 25 years, the most commonly used chemotherapy protocol for the prevention of metastases from malignant breast cancer in dogs was Adriamycin at 30mg/M@ LV. every 21 days and oral Cytoxan at 50 mg every other day for 8 weeks or on day 3-6 of each 21 day cycle. For the past 8 years many oncologists, including myself, prefer to use mitoxantron (Novantrone™) at 6 mg/M@ as a first choice and then Adriamycin or Carboplatin at 300mg/M@ for resistant disease.

The selected drug is administered every 21 to 30 days for 4-6 treatments then every 5- 6 weeks for 4-6 treatments or more depending on the severity of the malignancy. Treatment with chemotherapy may reduce the ability of the circulating cancer cells to establish viable colonies in the lungs.

In my practice, we recommend the supplements that are shown to reduce the risk of breast cancer for women: Inositol hexaphosphate (IP6 derived from rice), 1-3-beta glucan (derived from yeast) and [name witheld at request of producer], which contains the sugar, fucose, which is deficient in breast and prostate cancer patients. It makes 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” (see VPN, March 2000) supplements are added to the diet, they may play a role in the prevention of recurrent breast tumors in predisposed dogs.

CLINICAL TRIALS

We are not aware of any clinical trials at this time.

CLINICAL TRIAL RESULTS
1: J Vet Intern Med. 2003 Jan-Feb;17(1):102-6.

Influence of host factors on survival in dogs with malignant mammary gland tumors.
Philibert JC, Snyder PW, Glickman N, Glickman LT, Knapp DW, Waters DJ.
Department of Veterinary Clinical Sciences, Purdue University School of Veterinary Medicine, West Lafayette, IN, USA. jphilibert@nevog.com

The purpose of our study was to determine if specific host factors, such as age at diagnosis, obesity, and hormone status, influence the prognosis of canine mammary gland carcinomas and to confirm if previously reported risk factors (ie, histologic subtype, tumor size, and World Health Organization [WHO] stage) were important in a large series of affected dogs. Ninety-nine female dogs with mammary gland carcinomas, no previous therapy, an excisional biopsy, and known cause of death were studied. No significant association with survival was noted for age at diagnosis (chronologic or physiologic), obesity, or hormone status (ie, spayed versus intact, regardless of time of being spayed). Of the tumor factors analyzed, the histologic subtype anaplastic carcinoma (P = .02), WHO stage I (P = .01), evidence of metastasis at the time of diagnosis (P = .004), and tumor size of 3 cm or smaller (P = .005) all significantly influenced survival. Dogs that were classified as having tumor-related mortality had a shorter postoperative survival compared to dogs that died of other causes (14 months versus 23 months; P = .03). In conclusion, histologic subtype, WHO stage, and tumor size remain important prognostic factors in canine mammary gland tumors. Further study of other prognostic factors is needed to determine which tumors are adequately addressed with local therapy only and which dogs may require adjuvant treatment with chemotherapy.

PMID: 12564734 [PubMed - indexed for MEDLINE]
2. J Vet Intern Med. 2000 May-Jun;14(3):266-70.
Effect of spaying and timing of spaying on survival of dogs with mammary carcinoma

Sorenmo KU, Shofer FS, Goldschmidt MH

Department of Clinical Studies and Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6010, USA.

The risk of developing mammary gland tumors in dogs is significantly decreased by ovariohysterectomy at an early age. However, previous studies have not found a benefit to ovariohysterectomy concurrent with tumor removal in dogs with established mammary gland tumors, suggesting that the progression of these tumors is independent of continued estrogen stimulation. The purpose of this study was to evaluate the effect of spaying and of the timing of spaying on survival in dogs with mammary gland carcinoma. Signalment, spay status and spay age, tumor characteristics, treatment. survival, and cause of death of 137 dogs with mammary gland carcinoma were analyzed. The dogs were classified into 3 groups according to spay status and spay time: intact dogs, dogs spayed less than 2 years before tumor surgery (SPAY 1), and dogs spayed more than 2 years before their tumor surgery (SPAY 2). Dogs in the SPAY 1 group lived significantly longer than dogs in SPAY 2 and intact dogs (median survival of 755 days, versus 301 and 286 days, respectively, P = .02 and .03). After adjusting for differences between the spay groups with regard to age, histologic differentiation, and vascular invasion, SPAY 1 dogs survived 45% longer compared to dogs that were either intact or in the SPAY 2 group (RR = .55; 95% CI .32-.93; P = .03). This study reveals ovariohysterectomy to be an effective adjunct to tumor removal in dogs with mammary gland carcinoma and that the timing of ovariohysterectomy is important in influencing survival.

PMID: 10830539 [PubMed - indexed for MEDLINE]

NOTE: Dr. Sorenmo and the other oncologists at the MJR-Veterinary Hospital of the University of Pennsylvania are unable to answer questions directly from owners.  However, please feel free to direct questions through the veterinary editor of OncoLink.  Owners with questions will either be directed to the appropriate resources or a new FAQ will be created if the
requested information is not readily available.

LINKS FOR MORE INFORMATION ON MAMMARY CANCER:

Angiogenesis Foundation

Wing and Wave Labradors

VetInfo

The Pet Center (This site is graphic)

Oncolink

Pet Education.com (By Drs. Foster & Smith)

ACKNOWLEDGMENTS

Many thanks and acknowledgment to Dr. Alice Villalobos, Editor-in-Cheif of the American Association of Human Animal Bond Veterinarians; Animal Oncology Consultation Service Coast Pet Clinic of Hermosa Beach, Inc. for enthusiatically granting us permission to use the above information. To read more about the wonderful work Dr. Villalobos has done in the field of animal oncology click here.

Canine Cancer Awareness gratefully acknowledges the University of Pennsylvania Cancer Center ( OncoLink) for granting us permission for the use of the above information.

 PubMed , Published for MEDLINE, National Library of Medicine