ESR1 and metastatic neoplasm: A recent study showed that ERBB2-activating mutations occur with increased frequency in metastatic breast cancers; in fact, 70% of the ERBB2 mutations are detectable in HER2+ER+ non-amplified breast cancers, with a higher frequency occurring in metastatic tumors (4.3%) compared to primary cancers (2.5%) [104].