To determine whether genetic mutations in ESR1 and TCF7L2 influence their transcriptional activity, we applied a protein–protein interaction (PPI)-based deconvolution approach to two cohorts with matched mutation and RNA-seq data: a metastatic breast cancer cohort (n = 379)16 and TCGA-COAD (GDC dataset). This evidence concerns the gene TCF7L2 and breast cancer.