ERBB2 and breast carcinoma: Finally, the mechanistic basis of the HER2 genetic heterogeneity documented in this study remains to be defined; it should be noted, however, that this study provides direct evidence to demonstrate that a known driver and clinically actionable somatic genetic alteration (that is, HER2 gene amplification) can be heterogeneously distributed within breast cancers classified as HER2-positive by clinical definitions.