Mammary Tumor

Definition

Mammary fibroadenoma: A fibrous, benign, epithelial tumor in which cells are derived from glandular tissue.

Mammary adenocarcinomas: A malignant growth in glandular organs and arising from epithelium.

Clinical Signs

Typically seen as a soft, circumscribed (round), or somewhat flat appearing growth that can be movable on palpation, to a more firm and attached growth (seen more in malignancy) anywhere along the region of mammary tissue.
Impaired mobility as the growth becomes larger.
Ulceration and necrosis of tissue in later stages.
Increased appetite with no weight gain as dietary intake is redirected to tumor growth.
Poor appetite, weight loss, and lethargy as involvement progresses.
Development of one or more growths along mammary chain.

*Note: for information on recognizing various signs of pain or discomfort refer to: Signs of Pain In Rats.

Etiology

Mammary tissue is extensive in both female and male rats and is found ventral, lateral and dorsal, running from the shoulder and chin area to the base of the tail. However, as testosterone is released in the male rat fetus before mammary tissue development occurs the mammary glands are rudimentary, and they do not have nipples.

Tumors can arise anywhere that mammary tissue type is present but is most often seen at the pit of the arm, abdomen, and groin of female rats. Although mammary tumors can occur at a younger age, they have a higher occurrence after 18 months of age. These tumors may also occasionally present in males.

The most common mammary tumor found in rats is the mammary fibroadenoma, a benign encapsulated tumor. Rats do well when having these tumors removed, especially since the tumor tends to remain localized and is less invasive. Even though these tumors can be successfully removed they do tend to reoccur.

Mammary adenocarcinomas are firmer, more attached, and are less common than fibroadenomas. They not only invade surrounding organs but can metastasize by traveling through lymph and blood vessels to lungs and bone and can result in seeding other areas of the body.

Several factors appear to play a role in the development of spontaneous mammary tumors in the rat such as age, sex, genetics, endocrine, environment, and diet (Percy, Barthold, 2001).

Studies have shown that of those factors the most important influence in tumorigenesis is diet. It is well known that caloric intake affects tumor incidence in rats. Rats fed ad libitum (free-fed) have lower survival and a higher incidence of pancreatic, mammary, and pituitary tumors than rats fed a moderate dietary restriction of identical diets (Boorman & Everitt, 2006). In addition to increasing tumor incidence, high caloric intake decreases latency and enhances tumor growth (Keenan et al, 1995). Tumors with endocrine influence such as pituitary and mammary gland have been most severely altered by ad libitum feeding (Boorman & Everitt, 2006).

The development and growth of mammary tumors are primarily dependent on estrogen and prolactin (hormones controlled by the pituitary gland and the hypothalamus) receptor concentrations. The concentrations of these hormones are found to be higher in hormone dependent tumors, whereas in hormone independent tumors (as seen in latter stages of mammary adenocarcinoma) they tend to be lower. In addition, benign tumors (fibroadenomas) exhibit growth primarily due to increased influence of circulating prolactin. Studies show that spaying female rats, more specifically performing ovariectomy, can inhibit or reduce the development of those tumors influenced by prolactin and estrogen (Mietes, 1972; Hotchkiss, 1995; Russo & Russo,1998).

Although most mammary tumors in rats are benign, if not treated will continue to grow becoming quite large measuring from several millimeters to several centimeters and encompassing up to half the body weight of the rat. These tumors just by virtue of how large they can grow will not only impinge on other organs, but also inhibit the rat’s mobility, result in difficulty grooming, and interfere with the rat’s ability to feed itself. Weight loss eventually occurs as the tumor’s growth deprives other tissues and organs of needed nutrients. In addition, as these tumors continue to expand, they can eventually ulcerate, and bleed, causing anemia. Also, as the tumor becomes necrotic it can release toxins into the blood, leading to toxemia and septicemia ultimately resulting in organ failure and death.

Early removal of the tumor, even if malignant, can often extend the rat’s life. Even debulking a tumor, if not able to remove due to its involvement, may afford the rat more comfort and improve mobility.

Figures

Case Histories and Photos of Mammary Tumors

Fig. 1: Palpation of tumor
Fig. 2: Post-op incision site (Pooka)
Fig. 3: Large mammary tumor. *Note: contains postmortem and necropsy photos, very graphic.*
Fig. 4: Mammary tumor removal in 2.5-year-old female rat (photos of surgery included)
Fig. 5: Mammary adenocarcinoma in 1-year-old female rat (Petunia)
Fig. 6: Mammary tumor removal in 2-year-old female rat (Mus)
Fig. 7: Mammary tumor removal with dehiscence in female rat (Merel)
Fig. 8a: Mammary tumor removal with postop abscess in female rat (Muys)
Fig. 8b: Mammary tumor removal, postop abscess, and subsequent mammary tumors in female rat (Muys)
Cysts Fig. 3: Massive follicular/retention ovarian cyst and mammary tumors in 2.6-year-old female rat (Charlotte)

Video

A video presentation, Mammary Tumor Removal (USA), by Dr. J.C. Burcham DVM can be viewed in the Surgical section of the Rat Guide.

Diagnostics

Palpation of ovoid, discoid, or varied shaped mass. May be well demarcated.

Large mass may show ulceration or necrosis.

Rat may appear cachectic as tumor continues to grow.

Magnetic Resonance Imaging (MRI), for small animals (if available), may be useful with soft tissue tumors.

Histologic examination of tissue.

Microscopic examination of aspirate.

Treatment

Excision and removal of tumor is recommended. Note: preanaesthetic fasting of rats is not necessary since vomiting does not occur in this species. Free access to both food and water should be provided until just prior to anesthesia (Flecknell, 1991).

Pre- or post-op prophylactic broad-spectrum antimicrobials may be indicated in elderly, debilitated or immunocompromised rats.

Rats do experience pain with surgical procedures. The type of pain medication used post-op should be determined based on extent of procedure and the anticipated severity of pain.

For severe pain or first 24 hours post-op: Buprenex (buprenorphine), or Torbugesic (butorphanol).
For mild to moderate pain : Banamine (flunixin meglumine), Metacam (meloxicam), or carprofen. Do not use if a corticosteroid has already been prescribed.

*Note: for pain not controlled by the use of an NSAID (e.g., Banamine, meloxicam, or carprofen), alone, consider alternating or co-administering with a narcotic (e.g., buprenorphine or butorphanol) or narcotic-like (e.g., tramadol) medication.

For information regarding medications refer to the Rat Medication Guide.

Additional Considerations

If surgery for mammary tumor removal is being performed on female rats it is worthwhile to discuss with the vet the possibility of also spaying if the rat’s general health status is good. Since benign mammary tumors are hormone dependent, and malignant mammary tumors are initially hormone dependent, spaying females will significantly reduce or remove those hormones that influence these tumors.

Tamoxifen for malignant estrogen dependent tumors may be a treatment of choice in elderly rats with additional high risk health problems, or where surgery is no longer an option. *Note: Tamoxifen is not effective where hormone independent malignant tumors are present, or where benign tumor growth is due to circulating prolactin.
Where there has been removal of existing benign (adenoma) mammary tumors, a prolactin secretion inhibitor such as cabergoline, bromocriptine, or Melatonin (Sánchez-Barceló et al., 2003) for the prevention of new benign tumor growth may be beneficial.

Euthanasia should be considered, if tumor(s) affect the rat’s quality of life, after treatment options have been exhausted.

Nursing Care

Provide hospital cage during recovery, or if there are concerns that their cage mates may groom sutures or wound site.
Provide clean bedding daily such as felt, soft t-shirt type material or ink-free paper towels. Avoid using material such as terry cloth type towels that can ravel. Also avoid litter-type bedding, post-op, until healed to prevent the chance of wound contamination or infection.
Provide additional warmth to maintain body temperature within normal limits. It is essential that the rat does not become overheated or dehydrated. The rat should also be able to move away from the heat source if it becomes uncomfortable. If the rat is unconscious or immobile extreme care must be taken to keep the heat low and stable.
- You can use an isothermic product that is heated in the microwave such as SnuggleSafe®. Make sure to follow the product directions carefully and wrap in a towel before placing in the cage. SnuggleSafe® will provide heat for 12 hours before needing to be reheated. Other similar types of products may vary in re-heat time. Check directions for individual product.
- If using a heating pad (good for long term use) use only the low heat setting, put a thick towel in between the pad and the cage bottom, and place beneath a corner of the cage.
- If none of these options are available you can use a plastic bottle filled with hot water, and wrapped in a towel, in the corner of the cage.
Medicate for post-op pain as needed.
Body wrap may be required if thread sutures are used.
In the event of dried or excess drainage, the incision site may be cleaned with a moistened Q-tip (swab), using warm water or normal saline.
Contact veterinarian if any of the following are observed: swelling, redness, or pain at the incision site, or if there are signs of increased weight loss, lethargy, or changes in habits.
For 24 to 48 hrs post-op, feed iron-rich foods to prevent anemia (cooked liver, scrambled or hard-boiled eggs).
During recuperation provide additional high calorie foods or food supplements such as Nutri-Cal Paste, canned Ensure, soy or soy formula. Include multi-vitamin supplement (can be found in pet store) if food intake is poor.
Encourage fluid intake while recuperating, such as water, Jell-O water, or electrolyte replacement drinks such as Pedialyte or Gatorade (which can be found in local grocery stores).
- Please note that Pedialyte is only good refrigerated for 24 hours after opened, but can be frozen as ice cubes and thawed as needed.
- *Note: a juicy type of fruit also provides an additional fluid source in the diet.

Outcome

Post-op pain is relieved.
Incision site is free from infection.
Medication regimen given if deemed appropriate.
Increased comfort, mobility, and quality of life.
Weight loss is prevented.
Emotional support for those having to consider euthanasia for their rat.

Prevention

Offering a diet that is nutritiously low in fat, calories, amines, and nitrates is recommended.
Consideration should be given to spaying female rats. Documentation supports that ovariectomy prevents, or reduces frequency of, the development of spontaneous mammary tumors.
Routine health checks will aid in early detection of mammary tumors. Detection and treatment while the growth is still small decreases operative time, enhances recovery period, and improves outcome.

References

Boorman, G., Everitt, J. (2005). Neoplastic Disease. In M. Suckow, S. Weisbroth, & C. Franklin (Eds.), The Laboratory Rat, Second Edition (American College of Laboratory Animal Medicine). Toronto: Academic Press.
Hotchkiss, C. (1995). Effect of surgical removal of subcutaneous tumors on survival of rats. J Am Vet Med Assoc, 206(10), 1575-9. Retrieved January 1, 2009, from the Medline database.
Meites, J. (1972). Relation of prolactin and estrogen to mammary tumorigenesis in the rat. J Natl Cancer Inst, 48(4), 1217-24. Retrieved January 1, 2009, from the Medline database.
Russo, I., & Russo, J. (1998). Role of hormones in mammary cancer initiation and progression. J Mammary Gland Biol Neoplasia, 3(1), 49-61. Retrieved January 1, 2009, from the Medline database.
Sánchez-Barceló, E., Cos, S., Fernández, R., & Mediavilla, M. (2003). Melatonin and mammary cancer: a short review. Endocr Relat Cancer, 10(2), 153-9. Retrieved January 1, 2009, from http://erc.endocrinology-journals.org/cgi/reprint/10/2/153.pdf.
Creasy, D. (2008, March 8). Part 4: Mammary gland. Histopathology guidance document: endocrine disruption: guidelines for histological evaluation. Retrieved March 2, 2012, from http://www.oecd.org/dataoecd/57/7/40613059.pdf
Cardy, R. (1991). Sexual dimorphism of the normal rat mammary gland. Vet Pathol, 28(2), 139-45. Retrieved March 2, 2012, from http://vet.sagepub.com/content/28/2/139.full.pdf