Abstract
Breast cancer is the most common cause of cancer-related deaths in women worldwide. Identification of reliable prognostic indicators and therapeutic targets is critical for improving patient outcome. Cancer in companion animals often strongly resembles human cancers and a comparative approach to identify prognostic markers can improve clinical care across species. Feline mammary tumors (FMT) serve as models for extremely aggressive triple negative breast cancer (TNBC) in humans, with high rates of local and distant recurrence after resection. Despite the aggressive clinical behavior of most FMT, current prognostic indicators are insufficient for accurately predicting outcome, similar to human patients. Given significant heterogeneity of mammary tumors, there has been a recent focus on identification of universal tumor-permissive stromal features that can predict biologic behavior and provide therapeutic targets to improve outcome. As in human and canine patients, collagen signatures appear to play a key role in directing mammary tumor behavior in feline patients. We find that patients bearing FMTs with denser collagen, as well as longer, thicker and straighter fibers and less identifiable tumor-stromal boundaries had poorer outcomes, independent of the clinical variables grade and surgical margins. Most importantly, including the collagen parameters increased the predictive power of the clinical model. Thus, our data suggest that similarities with respect to the stromal microenvironment between species may allow this model to predict outcome and develop novel therapeutic targets within the tumor stroma that would benefit both veterinary and human patients with aggressive mammary tumors.
Highlights
Breast cancer is a significant cause of morbidity and mortality in both human and veterinary patients
To investigate which clinical parameters obtained from medical records at the time of diagnosis could predict survival in our cohort of patients with feline mammary tumors (FMT), we examined whether Grade category (I/II vs III), mitotic count, lymphatic invasion, tumor diameter, lymph node metastases at diagnosis, or surgical margins were associated with the outcomes, Survival time (ST) or Disease-free survival (DFS) using Cox regression univariate analysis (Table 1)
After previously defining collagen characteristics that could predict outcome in canine mammary tumor patients, we hypothesized that collagen plays a critical role in directing the biologic behavior of FMT and certain collagen signatures could predict clinical outcomes in these feline patients
Summary
Breast cancer is a significant cause of morbidity and mortality in both human and veterinary patients. Dogs and cats, resembles cancer in humans in various ways, including: (1) its multifactorial nature, including both genetic and environmental risk factors; (2) its latency, clinical manifestation and metastatic potential; (3) its histopathologic features, including tumor cell heterogeneity and permissive microenvironment; and (4) shared prognostic markers and response, as well as resistance to therapeutics. Despite the fact that a relatively large number of studies have attempted to identify prognostic markers and therapeutic targets (more than 200 papers have been published on FMT) [9], FMT remains one of the most common causes of cancer-related deaths in older female cats, similar to women [10]. FMT are ideal models for extremely aggressive TNBC human breast cancers, as most FMT are hormone-receptor negative [14]. Due to the aggressive nature of these tumors, early detection and more effective treatment options are critical for preventing metastasis, and improving survival time [17, 18]
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