Malignant mammary tumors: Biologic behavior, prognostic factors, and therapeutic approach in cats - Veterinary Medicine
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Malignant mammary tumors: Biologic behavior, prognostic factors, and therapeutic approach in cats
Most mammary tumors in cats are malignant, and metastasis is common. The prognosis depends on how far the cancer has spread and the tumor's biologic behavior, among other things. Find out how to improve the outcome in these critically ill cats.


VETERINARY MEDICINE


Metastasis


Figure 6. A lateral thoracic radiograph of a cat presenting for evaluation of dyspnea of one weeks duration. Past pertinent history included surgical resection of a mammary tumor nine months earlier. Radiographic findings are consistent with moderate to severe pleural fluid accumulation and multiple soft tissue metastatic lesions (white arrows).
Clinical evidence of distant metastasis is a negative prognostic factor.12,26 Pulmonary metastasis is the most common cause of mammary-carcinoma–related deaths, and cats presenting with advanced lung involvement at diagnosis have a reported median survival time of only one month (Figure 6).8,16 The location of metastatic disease is a significant prognostic factor for both disease-free interval and median survival time, with cats with metastatic disease in regional lymph node, pulmonary, and pleural anatomic sites having a median survival time of 1,543, 332, and 188 days, respectively.43 In addition to the negative impact of distant metastasis, it has been anecdotally reported that cats with histologic evidence of lymphatic invasion have a median survival time of seven months compared with 18 months in cats without lymphatic invasion.50 Likewise in male cats with mammary carcinoma, lymphatic invasion is also a negative prognostic factor, with a median survival time of 195 days vs. 863 days in tumors positive or negative for lymphatic invasion, respectively.10

Histologic criteria

Histologic grade appears to be inversely correlated with prognosis and survival time. Although low-grade tumors are less common (13% prevalence), most cats with low-grade tumors survive for more than one year, while only 10% of cats with high-grade tumors are alive one year after surgical resection alone.41 Histologic subtype is prognostic for disease-free interval, with papillary or tubular, ductular, and anaplastic tumors having a disease-free interval of greater than 1,131, 306, and 95 days, respectively.43

In addition to tumor grade, the prognostic utility of other histologic criteria has been evaluated individually. Proliferative indices, including proliferating cell nuclear antigen (PCNA), argyrophilic nucleolar organizer regions (AgNORs), and Ki-67 nuclear antigen, have been evaluated in feline mammary carcinomas. PCNA was higher in malignant tumors, reflecting greater mitotic activity.51 In two other clinical studies, increased AgNOR counts in malignant mammary tumors correlated with shorter postsurgical survival times.9,26 However, the relevance of Ki-67 nuclear antigen in feline mammary malignancies is unclear, as there is an inconsistent relationship between Ki-67 expression and either clinical outcome or grade.40,52,53 Thus, feline mammary tumors with greater mitotic activities, as reflected by greater PCNA and AgNOR counts, may possess more aggressive biologic behaviors.

Finally, similar to human breast cancer patients, the histologic identification of HER2 protein expression in cats with mammary carcinoma has also been identified as a negative prognostic factor.23

Molecular markers

Other factors associated with malignant transformation and clinical outcome have been evaluated, including various molecular markers. Both vascular endothelial growth factor (VEGF), an angiogenic factor involved in new blood vessel formation, and tumor microvessel density are routinely used to assess neoplastic angiogenesis. While mammary tumor microvessel density is not associated with survival or prognosis, increased mammary carcinoma VEGF expression has been associated with a worse clinical outcome.27 Aberrant expressions of other molecular markers that do not appear to provide direct prognostic information in feline mammary carcinoma include reduced E-cadherin, overexpression of bcl-2, and mutations in p53.54-58 These diagnostic tools are being evaluated in a research setting.

SUMMARY

Malignant mammary neoplasia is a common tumor affecting cats, with a well-described clinical course and documented risk factors. Although the efficacies of adjunctive treatments such as chemotherapy, radiation therapy, and immunotherapy are being investigated, the mainstay of current treatment is aggressive surgical intervention. Accepted prognostic factors include tumor size, extent of surgery, histologic grade, and presence of metastatic disease. Current research focuses on delineating the biologic pathways involved in malignant transformation in the hopes of providing new preventive, diagnostic, and therapeutic options for our feline patients.

Jackie Wypij, DVM
Timothy M. Fan, DVM, DACVIM (oncology, internal medicine)
Louis-Philippe de Lorimier, DVM, DACVIM (oncology)
Department of Veterinary Clinical Medicine
College of Veterinary Medicine
University of Illinois
Urbana, IL 61802


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