In strong support of the notion of CAFs as modifiers of the malignant phenotype, the vCAF gene signature was found to be an independent prognostic indicator associated with an increased risk for developing metastatic disease in both univariable and multivariable analysis in a conditional logistic regression model involving common risk factors such as lymph node status, tumor size, HER2 status, and proliferative index (Table 1). This evidence concerns the gene HCFC1 and metastatic neoplasm.