This trend was modest in our exploratory case series (p = 0.1), but given that most HER2+ breast cancer patients are now treated in the first-line setting with trastuzumab and pertuzumab, and that intracranial disease is relatively insensitive to HER2 therapy [12,13,14,15,16], larger cohort studies would be warranted to investigate HER2-HER3 dimerization in relation to acquired resistance, and whether this can be suppressed by pertuzumab and/or anti-HER3 mAbs in the metastatic setting. The gene discussed is ERBB3; the disease is breast cancer.