The first clinical evidence that coupled the expression of the d16HER2 variant with tumor progression and metastasis was reported in 2009 by Mitra and colleagues, who showed that 89% of patients with HER2-positive BC that coexpressed the d16HER2 variant presented with positive lymph nodes on diagnosis versus 12% of d16HER2-negative BCs [24]. This evidence concerns the gene ERBB2 and neoplasm.