Preclinical findings have provided clear evidence that resistance to trastuzumab and lapatinib can occur spontaneously following EMT as HER2+ BC cells shift from a luminal to a basal/mesenchymal phenotype with high enrichment of CD44high/CD24low BCSCs and inherent EMT traits [108]; specifically, preclinical evidence has highlighted a relevant increase in Slug, Twist1 and ZEB1 expression levels in trastuzumab-refractory basal/HER2+ cells versus trastuzumab-susceptible luminal/HER2+ cell models [109]. The gene discussed is TWIST1; the disease is breast cancer.