These findings, together with ourcurrent description that a) ATG12 overexpression is a new molecular biomarker for primary resistanceto trastuzumab and b) inherent unresponsiveness to trastuzumab can be switched to sensitivity simplyby depleting ATG12 notably delineates a new scenario in which primary resistance to HER2-targeteddrugs can be understood in terms of HER2 gene-amplified breast carcinoma cells thatare intrinsically capable of generating highly autophagic, undifferentiatedCD44+CD24−/low antigenic states. The gene discussed is ATG12; the disease is breast carcinoma.