Mammary tumors are one of the most common types of feline cancer and are particularly prevalent in intact female cats. Surgical excision is the treatment of choice; however, the role of adjuvant chemotherapy remains controversial. The prognosis is highly dependent on clinical staging, which is recommended before treatment begins.
Etiology of Mammary Tumors in Cats
It is estimated that 80%–90% of mammary tumors in cats are malignant (1), whereas in dogs, a much higher percentage (around 50%) of mammary tumors are benign (2). Most mammary tumors in cats are malignant epithelial tumors (ie, carcinomas), with the most common subtypes being simple tubular carcinomas, tubulopapillary carcinomas, and solid carcinomas (3).
Like dogs, cats exposed to ovarian hormones are at an increased risk for developing mammary tumors. The protective effect of ovariohysterectomy rapidly decreases as cats age, with spaying having no benefit after age 2 years. However, cats spayed before 6 months have a 91% decreased risk of mammary tumor development; those spayed before 12 months have an 86% decreased risk (4). Administration of exogenous progestins can also lead to mammary tumor development in both male and female cats (5, 6).
Pearls & Pitfalls
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Age and breed have also been identified as possible risk factors for the development of mammary tumors, with older and purebred cats being overrepresented (1, 7, 8).
Clinical Findings of Mammary Tumors in Cats
Cats have 4 pairs of mammary glands, with some reports suggesting that mammary tumors affect the caudal mammary glands more commonly, although this has not been definitively established (8). It is not uncommon for cats to develop multiple mammary tumors, so all mammary glands should be carefully palpated in cats with mammary masses or with a history of mammary tumors (9).
Mammary masses are located in the subcutaneous tissues within or around mammary glands. Mammary tumors are typically firm and variably sized, ranging from very small mobile nodules to larger fixed, ulcerated masses. The local/sentinel lymph nodes—which are usually the axillary and inguinal lymph nodes, depending on the location of the primary mammary mass—may be enlarged (10).
Mildly enlarged or normal-sized lymph nodes, which are often not palpable in cats, do not rule out metastatic disease. Cats can otherwise be clinically normal even with advanced disease, with almost 50% of cats with distant metastasis from mammary tumors showing no clinical signs of illness (11).
Diagnosis of Mammary Tumors in Cats
Cytological evaluation
Histological evaluation
After a mammary mass is detected, cytological evaluation can provide a tentative diagnosis, although histological evaluation is required for definitive diagnosis. Fine-needle aspirates for cytological testing are cheaper and less invasive and carry less morbidity than a biopsy; depending on the patient, they may be collected without sedation. Cytology is usually sufficient to confirm the cell line and to determine whether a mass is neoplastic; however, cytology may be insufficient to determine whether a neoplastic lesion is benign or malignant. Given that most feline mammary tumors are malignant and surgery is likely to be recommended, determining whether the mass is malignant preoperatively is generally less important.
Intact cats can also have mammary enlargement or masses secondary to mammary hyperplasia, which typically resolves with ovariohysterectomy.
Once histological results are available, feline mammary carcinomas can be graded similarly to canine mammary carcinomas using the Elston and Ellis grading system based on tissue differentiation, nuclear pleomorphism, and mitotic count (12). Higher tumor grade is associated with poorer prognosis, with cats diagnosed with grade III mammary carcinomas exhibiting significantly shorter median survival times compared with those with grade I tumors (13, 14).
Staging
Full staging is recommended before any treatment, given that most feline mammary tumors are malignant and stage of disease substantially impacts both treatment and prognosis. In addition, staging allows screening for concurrent diseases that might influence not only prognosis, but also the degree to which treatment will be tolerated.
The staging system most commonly applied to cats with mammary tumors is adapted from the WHO staging system (15, 16). Stage advances as the size of the primary tumor increases, from < 2 cm (stage I), to 2–3 cm (stage II), to > 3 cm (stage III). Regardless of tumor size, lymph node involvement also represents stage III disease, and distant metastasis constitutes stage IV disease. Evaluation of the primary tumor's diameter is very helpful in establishing prognosis because larger tumors (> 3-cm diameter) carry a worse prognosis than smaller tumors.
Staging of Feline Mammary Tumorsa
Stage | T | N | M |
|---|---|---|---|
I | T1 | N0 | M0 |
II | T2 | N0 | M0 |
III | T1, T2 T3 | N1 N0, N1 | M0 M0 |
IV | Any T | Any N | M1 |
Abbreviations: M, distant metastasis; M0, no distant metastasis; M1, distant metastasis present; N, nodal involvement; N0, no nodal metastasis present; N1, nodal metastasis present; T, size of primary tumor; T1, tumor < 2 cm; T2, tumor 2–3 cm; T3, tumor > 3 cm. a Adapted from the World Health Organization staging system. | |||
The staging process should include hematologic and biochemical testing, as well as urinalysis, because most cats with mammary tumors are elderly and may have concurrent disease. The local/sentinel lymph nodes and the lungs are the most common sites for metastasis, although abdominal organs and other lymph nodes can also be affected. As such, imaging is a crucial part of staging and should include both thoracic and abdominal imaging (typically thoracic radiography or CT and abdominal ultrasonography).
Fine-needle aspirates of local lymph nodes should also be performed because normal-sized lymph nodes do not exclude metastatic disease. If local lymph nodes cannot be palpated, ultrasonography can be used to direct fine-needle aspiration.
Treatment of Mammary Tumors in Cats
Surgery
Chemotherapy
Surgery
Surgery is the treatment of choice for cats with mammary tumors. In addition to the obvious therapeutic benefits, surgery also allows tissue collection for histological examination and determination of a definitive diagnosis.
Multiple surgical approaches exist; however, surgical approach appears to impact prognosis, with full-chain mastectomy associated with a longer disease-free interval compared with regional mastectomy (17). In addition, bilateral full-chain mastectomy has also been associated with lower risk of local recurrence and metastasis compared with unilateral full-chain mastectomy. However, bilateral full-chain mastectomy performed during a single procedure can carry higher morbidity compared with staged bilateral mastectomies (18).
Chemotherapy
Although surgery generally leads to good local control of disease, feline mammary tumors are typically malignant and systemically aggressive, so most cases are not adequately treated just with surgery. However, there is no definitive evidence suggesting that use of adjuvant chemotherapy improves outcome, so the literature remains inconclusive on this topic.
Most studies evaluating the use of adjuvant doxorubicin (1 mg/kg, IV, every 3 weeks, for a maximum of 5 treatments) in the treatment of feline mammary tumors have failed to show increased survival rates over treatment with surgery alone (19, 20), with few reports suggesting a possible benefit (16, 21). Although available data do not support this practice, many veterinary oncologists recommend adjuvant chemotherapy for treatment of cats either with advanced stage (lymph node or distant metastasis) mammary neoplasia or with tumors showing histopathological features of aggressive biological behavior.
In the treatment of feline metastatic mammary carcinoma, administration of the tyrosine kinase inhibitor toceranib, which has antiangiogenic effects, was not associated with any survival difference when compared with treatment with maximum tolerated dose chemotherapy or metronomic chemotherapy; however, this study was retrospective and involved only a small number of cases in each treatment group (11). Toceranib has a favorable toxicity profile and is generally well-tolerated, so it is a valid option in the treatment of cats with advanced mammary carcinoma.
Prognosis of Mammary Tumors in Cats
Given the aggressive nature and high metastatic potential of feline mammary carcinoma, the prognosis remains guarded. Of several clinical prognostic factors that have been identified, tumor size and lymph node metastasis, which can be evaluated during staging, are particularly important.
Survival rates correlate inversely with tumor diameter, with cats harboring tumors < 2 cm, 2–3 cm, and > 3 cm displaying median survival times exceeding 3 years, 2 years, and 6 months, respectively (17). However, an alternative study reported a median survival time of 12 months for cats with mammary tumors > 3 cm, contrasting with 21 months for those with smaller tumors. Notably, a wide range (3–54 months) of survival times was observed among cats with smaller tumors, indicating additional influencing factors beyond tumor size (22).
Consistent evidence underscores lymph node metastasis as a significant adverse prognostic factor (13, 18). In one study, all cats with lymph node metastasis at the time of surgery developed progressive disease within 8 months, highlighting the predictive value of metastasis (13). However, as previously mentioned, bilateral mastectomy demonstrated protective effects against disease progression, even in cases where local lymph nodes were metastatic, which suggests a positive impact of surgical approach on prognosis (18).
Overall clinical stage, which considers tumor size, lymph node involvement, and distant metastasis, is predictably associated with survival time. Cats with stage IV disease exhibit notably short median survival times of 44 days (11, 13, 19). In addition, the location of metastasis influences prognosis in cats with mammary adenocarcinoma. Cats with nodal, pulmonary, and pleural metastasis have progressively worse median survival times, as evidenced in a study of cats treated with surgery and adjuvant doxorubicin (21).
Although findings across studies often conflict, other factors besides clinical stage, such as age and breed, inconsistently impact prognosis, with older and purebred cats generally facing a worse prognosis compared with younger cats and domestic shorthair cats.
Histopathological analysis of tumor tissue, with particular emphasis on tumor grade, plays a crucial role in determining prognosis. Feline mammary carcinomas are graded using a system adapted from the Elston and Ellis grading system, akin to that used in dogs, which evaluates tissue differentiation, nuclear pleomorphism, and mitotic count (12).
Survival outcomes vary significantly based on tumor grade. For instance, cats diagnosed with grade I mammary carcinomas have a median survival time of 36 months, whereas those with grade III tumors have a considerably shorter median survival time of only 6 months (13). In addition, the 1-year mortality rates for grades I, II, and III mammary carcinomas stand at 0%, 42.4%, and 100%, respectively (14).
An alternative grading system, integrating vascular invasion rather than tubule formation, also has been proposed. This updated system demonstrates prognostic relevance, with median survival times for cats diagnosed with grades I, II, and III mammary carcinomas recorded as 31, 14, and 8 months, respectively (23).
Key Points
Mammary tumors are common in intact female cats.
Clinical stage impacts the prognosis of cats with mammary tumors, so early diagnosis and treatment can lead to improved survival times.
Surgical excision is the treatment of choice; the role of adjuvant chemotherapy is not well established.
References
Pickard Price P, Stell A, O'Neill D, Church D, Brodbelt D. Epidemiology and risk factors for mammary tumours in female cats. J Small Anim Pract. 2023;64(5):313-320. doi:10.1111/jsap.13598
Salas Y, Márquez A, Diaz D, Romero L. Epidemiological study of mammary tumors in female dogs diagnosed during the period 2002-2012: a growing animal health problem. PLoS One. 2015;10(5):e0127381. doi:10.1371/journal.pone.0127381
Sorenmo KU, Worley DR, Zappulli V. Tumors of the mammary gland. In: Vail DM, Thamm DH, Liptak JM, eds. Withrow and MacEwen's Small Animal Clinical Oncology. 6th ed. WB Saunders. 2019; 604-625.
Overley B, Shofer FS, Goldschmidt MH, Sherer D, Sorenmo KU. Association between ovariohysterectomy and feline mammary carcinoma. J Vet Intern Med. 2005;19(4):560-563. doi:10.1111/j.1939-1676.2005.tb02727.x
Skorupski KA, Overley B, Shofer FS, Goldschmidt, MH, Miller CA, Sørenmo KU. Clinical characteristics of mammary carcinoma in male cats. J Vet Intern Med. 2005;19(1):52-55.
Misdorp W, Romijn A, Hart AA. Feline mammary tumors: a case-control study of hormonal factors. Anticancer Res. 1991;11(5):1793-1797. https://pubmed.ncbi.nlm.nih.gov/1768052/
Hayes HM Jr, Milne KL, Mandell CP. Epidemiological features of feline mammary carcinoma. Vet Rec. 1981;108(22): 476-479. https://europepmc.org/article/med/7257136
Weijer K, Hart AA. Prognostic factors in feline mammary carcinoma. J Natl Cancer Inst. 1983;70(4):709-716. doi:10.1093/jnci/70.4.709
Hayes AA, Mooney S. Feline mammary tumors. Vet Clin North Am Small Anim Pract. 1985;15(3):513-520. doi:10.1016/S0195-5616(85)50054-6
Papadopoulou PL, Patsikas MN, Charitanti A, et al. The lymph drainage pattern of the mammary glands in the cat: a lymphographic and computerized tomography lymphographic study. Anat Histol Embryo. 2009;38(4):292-299. doi:10.1111/j.1439-0264.2009.00942.x
Petrucci G, Henriques J, Gregório H, et al. Metastatic feline mammary cancer: prognostic factors, outcome and comparison of different treatment modalities: a retrospective multicentre study. J Feline Med Surg. 2021;23(6):549-556. doi:10.1177/1098612X20979892
Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19(5):403-410. doi:10.1111/j.1365-2559.1991.tb00229.x
Seixas F, Palmeira C, Pires MA, Bento, M.J, Lopes C. Grade is an independent prognostic factor for feline mammary carcinomas: A clinicopathological and survival analysis. Vet J. 2011;187(1):65-71. doi:10.1016/j.tvjl.2009.10.030
Castagnaro M, Casalone C, Bozzetta E, De Maria R, Biolatti B, Caramelli M. Tumour grading and the one-year post-surgical prognosis in feline mammary carcinomas. J Comp Pathol. 1998;119(3):263-275. doi:10.1016/S0021-9975(98)80049-2
TNM classification of tumours in domestic animals. Owen LN, ed. World Health Organization. 1980; 53.
McNeill CJ, Sorenmo KU, Shofer FS, et al. Evaluation of adjuvant doxorubicin-based chemotherapy for the treatment of feline mammary carcinoma. J Vet Intern Med. 2009;23(1):123-129. doi:10.1111/j.1939-1676.2008.0244.x
MacEwen EG, Hayes AA, Harvey HJ, Patnaik AK, Mooney S, Passe S. Prognostic factors for feline mammary tumors. J Am Vet Med Assoc. 1984;185(2):201-204. https://pubmed.ncbi.nlm.nih.gov/6746390/
Gemignani F, Mayhew PD, Giuffrida MA, et al. Association of surgical approach with complication rate, progression-free survival time, and disease-specific survival time in cats with mammary adenocarcinoma: 107 cases (1991–2014). J Am Vet Med Assoc. 2018;252(11):1393-1402. doi:10.2460/javma.252.11.1393
Ito T, Kadosawa T, Mochizuki M, Matsunaga S, Nishimura R, Sasaki N. Prognosis of malignant mammary tumor in 53 cats. J Vet Med Sci. 1996;58(8):723-726. doi:10.1292/jvms.58.723
Petrucci GN, Henriques J, Lobo L, et al. Adjuvant doxorubicin vs metronomic cyclophosphamide and meloxicam vs surgery alone for cats with mammary carcinomas: A retrospective study of 137 cases. Vet Comp Oncol. 2021;19(4):714-723. doi:10.1111/vco.12660
Novosad CA, Bergman PJ, O'Brien MG. Retrospective evaluation of adjunctive doxorubicin for the treatment of feline mammary gland adenocarcinoma: 67 cases. J Am An Hosp Assoc. 2006;42(2):110-120. doi:10.5326/0420110
Viste JR, Myers SL, Singh B, Simko E. Feline mammary adenocarcinoma: tumor size as a prognostic indicator. Can Vet J. 2002;43(1):33-37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC339085/
Mills SW, Musil KM, Davies JL, et al. Prognostic value of histologic grading for feline mammary carcinoma: a retrospective survival analysis. Vet Pathol. 2015;52(2):238-249. doi:10.1177/0300985814543198
