Supported by strong evidence in developmental, evolutionary, and cancer biology, we hypothesize that persistent EGFR–K-RAS–SIAH pathway activation is a major tumor-driving force in TNBC, and that SIAH is a new tumor-specific, therapy-responsive, and prognostic biomarker for patient risk stratification, therapy quantification, and treatment optimization[76,77,82-85,89]. The gene discussed is EGFR; the disease is cancer.