Building on these data, the ongoing single-arm, phase II BRIDGET trial (NCT05323955) is evaluating the addition of tucatinib to maintenance trastuzumab/pertuzumab or T-DM1 after local therapy for isolated brain metastases in patients with advanced HER2-positive breast cancer (23) By enrolling patients with stable extracranial disease after stereotactic radiosurgery and/or surgical resection, BRIDGET exemplifies a ‘secondary prevention’ strategy that aims to delay further intracranial progression through sustained BBB-penetrant HER2 blockade. Here, ERBB2 is linked to breast carcinoma.