Feline Mammary Adenocarcinoma (FMGAC)
by Dr. Alice Villalobos
SVMA SUN VALLEY '98

In the U.S.A., comparative statistics between cats and humans show that one in nine women will suffer from breast cancer in contrast to only 25 of 100,000 cats. Over 183,000 surgeries are performed every year on women to fight breast cancer. 43,000 women die every year and one in three have metastatic lesions in the brain at death. Incidence IN CATS

FMGAC is the third most common tumor in cats after hematopoietic and skin tumors are considered. Cats experience breast cancer risk in a ratio of 50% less rick than dogs. Histopathology finds that 86% of tissues sent from feline mammary gland excisions are malignant adenocarcinomas and less frequently sarcomatous. Intact cats are at greater risk of developing FMGAC at 31.8 of 100,000 cats. OVH cats show less risk at 20.4 of 100,000.

The average age at onset is 10-14 years with a range as young as nine months to 23 years. The mean age is 10-12 years in several studies. Siamese cats may be regarded as being at two times greater risk than other cats. And sadly, the Siamese as a breed alone also develops their FMGAC at a younger age. Next at risk are Domestic Short Hair cats who are intact followed by spayed females. FMGAC very rarely involves male cats. COMMON MANAGEMENT MISTAKES

It is a definite mistake on the part of any practitioner to take a "wait and see" attitude, postpone a work up or waste precious time on any beloved cat that presents with mammary nodules or cysts. Cats with breast nodules must be automatically considered at a 90% or greater risk for malignancy. Tubular, papillary and solid carcinomas are the most common histologically malignant forms of FMGAC, but most tumors have a combination of tissue types in the same cat. Biopsy reports will vary and some will find the less common types of duct papillomas, sarcomas, mucinous carcinomas adenosquamous carcinomas and adenomas. ETIOLOGY

The etiology of FMGAC remains multifactorial. Most researchers agree that MGAC causation may originate in the milieu of hormonal influences on pathogenesis. Verification has been found in hormone receptor research work in women and dogs but less so in cats. Cats have lower levels of detectable hormone and this makes research frustrating in this species. A 1971 study suggested that intact dogs and cats had a seven fold increased risk of FMGAC, but other studies did not substantiate this work. Rarely one will see a young, intact female cat with huge mammary masses which are benign. This condition is known as fibroepithelial hyperplasia and should not be mistaken for FMGAC. IATROGENIC FACTORS

The role of progesterone, testosterone and estrogen have been investigated in cats. Only 10% of FMGAC were found to have estrogen receptors while humans and dogs have a much higher level of positive receptors. It seems that prolonged progesterone levels play an influential part in causation of FMGAC. Megase, ovaban, depoprovera and other progesterone-like drugs were frequently used in cats for miliary dermatitis or behavior problems. Later on these drugs were associated with the development of FMGAC or benign mammary hyperplasia and documented in the '70's by 12 veterinary colleges. Cats that have cystic ovaries and other uterine disorders are more likely to develop breast cancer than healthy queens. History and Symptoms

Unfortunately cats with bumps look and feel fine so many pet owners don't think bad thoughts. One study in 1978 found that most cats may have had their mammary masses noted over five months before visiting the veterinarian. Cats present with locally invasive nodules which may be firm moveable or fixed to the abdominal wall and overlying skin. About 25% have ulcerations and most have micrometastasis into the local lymphatics and near by lymph nodes. Often one can palpate the "beaded chain" appearance of involved lymphatics. Tumors close to the nipples may be expressed yeilding a tan or yellow liquid. Often there is swelling and discomfort and infection and mild fever. Involvement may be more often in the cranial two mammary glands or along the entire right or left chain with over 50% of cases involving more than one gland at presentation. A few cases may be associated with chronic mastitis or mammary cystic disease or uterine disorders. WORK UP AND STAGING

Remember that this cancer is very aggressive! Consultation should recommend x-rays, a profile, FNA of local nodes if enlarged, U/A and U/S. Direct the client toward a radical surgical excision of both chains one month apart if the cat is a good candidate. Three views of the chest are important to evaluate for pleural effusion and interstitial densities which may be faintly visible. Consultation with a radiologist may help to distinguish the difference between old cat lungs which may show aging changes and inactive inflammatory lesions that mimic the metastatic process. It is fair to tell your client that you feel the x-rays are equivocal yet vote to proceed with surgery. One can wait 7-12 days and take a second set of x-rays to see if the presumed lesions are stable PRIOR to a definitive surgery. PROGNOSIS IS ALWAYS GUARDED TO POOR

Unfortunately the recurrence rate of FMGAC that were surgically removed runs high (66%) and most afflicted cats are dead within one calender year. If tumors are smaller than 3cm, the cat has a better chance. If the tumor is 2-3cm, the data shows that cats can get a two year median survival. If the mass is 1cm and shows no lymphatic invasion the median survival is 3 years. So it makes sense to educate our pet owning public to jump when they first find lumps and ulcers in cats! TREATMENT FOR FMGAC

I prefer to coach the client into two radical chain mastectomies one month apart and one year of chemotherapy using mitoxantrone at 5.5mg/M2 every 21-30 days for one year. If the tumor is fixed to the wall, I prefer to use aggressive intraoperative techniques such as chemotherapy implants using carboplatinum and intraoperative radiation therapy. We have cases in which clients come to our service after several recurrences at a local site. The last thing they want is another surgery. Often the previous surgery was not definitive in that it did not remove the body wall which the tumor was in contact with nor was the local draining lymph node removed for histopathology. Radical surgery along with aggressive intraoperative technique can spare further surgery. Follow up intralesional chemotherapy implants are also very workable while systemic mitoxantrone or adriamycin chemotherapy is being administered. Cytoxan given at 10mg/kg divided over 2 days once at 21 days after adriamycin or mitoxantrone is helpful. Cytoxan can also be given at 1/2 of a 25 mg tablet every other day in 7-10 pound cats with safety while they are on the other chemotherapy agents. The seven and ten day nadir for these agents should be marked with a CBC to document the WBC and platelet count. If the cat feels fine and has no leukopenia, the follow up treatments may proceed with no change in dose. Taxol remains too toxic for use in private practice. Gene therapy and TALL-40 (activated WBC's) are still a reaseach mile away from every day use. A 50% short term response has been observed using chemotherapy; however, fmgac remains resistant in its advanced stages. The best results are seen in early cases that get bilateral mastectomies and one year of chemotherapy. An increased client awareness program in your practice and early aggressive case management is the key to successful outcome.