In this study we hypothesized that clinically metachronous brain metastasis from HER2-positive breast cancers would differ in their repertoire of somatic genetic alterations from their respective primary tumor, and that potentially targetable driver genetic alterations would be enriched in or restricted to the metastases, and could be employed as genetic biomarkers to guide the rational use of targeted agents. Here, ERBB2 is linked to breast carcinoma.