Finally, molecular activity prediction of the canonical pathway estrogen receptor signaling defined by the Ingenuity Knowledge Base included three of the six (TP53, PTEN, NOTCH1, AKT1, PIK3CA, and RB1) commonly downregulated genes with loss of function mutations in both molecular subtypes of breast cancer (TNBC and HER2−). The gene discussed is ESR1; the disease is breast carcinoma.