Patient-to-patient variability in breast cancer progression complicates clinical treatment decisions. Of women undergoing prophylactic mastectomies, many may not have progressed to indolent forms of disease and could have benefited from milder, localized therapy. Tumor associated macrophages contribute significantly to tumor invasion and metastasis, with cysteine cathepsin proteases as important contributors. Here, a method is demonstrated by which variability in macrophage expression of cysteine cathepsins, their inhibitor cystatin C, and kinase activation can be used to train a multivariate model and score patients for invasion risk. These enzymatic profiles were used to predict macrophage-assisted MCF-7 breast cancer cell invasion in the trained computational model. To test these predictions, a priori, signals from monocytes isolated from women undergoing mastectomies were input to score their cancer invasion potential in a patient-specific manner, and successfully predicted that patient monocytes with highest predicted invasion indices matched those with more invasive initial diagnoses of the nine patients tested. Together this establishes proof-of-principle that personalized information acquired from minimally invasive blood draws may provide useful information to inform oncologists and patients of invasive/metastatic risk, helping to make decisions regarding radical mastectomy or milder, conservative treatments to save patients from hardship and surgical recovery.

Sloan-Kettering Cancer Center cancer registry, Chipollini's 2017 multicenter study, National Cancer Database, and the Mayo Clinic's internal records. Multivariable linear analysis was performed evaluating comparative disease severity to survival.RESULTS: Data from TCGA was consistent with included studies' cohorts' mean age of onset (TCGA 60.57 compared to 61.07 AE 0.80 years). The female to male ratio for TCGA data was 0.55 compared to the mean of included studies of 0.50 AE 0.04. Mean follow up time for TCGA was shorter, at 37.50 months. Average follow up time for included studies was 40.27 AE 11.71 months, and ranged from 10.60 months to 94.80 months. Disease free survival (DFS) at five years for TCGA was 21.04%. The mean of existing data was 68.58% AE 14.11%, but the included studies had an average DFS range of 9.00% to 97.00%. ANOVA of DFS at five years and tumor staging was comparable, with a p-value of 3.91E-6. Average overall survival (OS) for TCGA was 28.68% at five years.CONCLUSIONS: TCGA kidney cancer cohort includes clinicopathological characteristics for more severe disease. Only 28.68% of the cohort survives past five years, falling between the average for stage III (53%) and stage IV (8%), short of the average 74.10%. The age of onset is earlier for TCGA cohort than the average 64 years. The female to male ratio is skewed more towards men. For tumor staging and five-year survival, TCGA shows consistency with other studies of disease progression. Data from TGCA can be considered representative of invasive kidney cancer and serve as a valuable resource to validate prognostic biomarkers.

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