Lin NU, Pegram M, Sahebjam S, et al. - Patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC) commonly develop CNS metastasis, however, there are limited systemic therapies effective against brain metastases. In phase II PATRICIA study, pertuzumab plus high-dose trastuzumab (6 mg/kg weekly) was tested in patients suffering from HER2-positive MBC with CNS metastases that had progressed post-radiotherapy. Confirmed objective response rate (ORR) in the CNS per Response Assessment in Neuro-Oncology Brain Metastases criteria, was the primary endpoint. CNS ORR was estimated to be 11%, with four partial responses (median duration of response, 4.6 months). At 4 months and 6 months, a clinical benefit rate of 68% and 51%, respectively, was obtained. Overall, modest CNS ORR was achieved, and clinical benefit was seen in 68% of patients, two patients experienced ongoing stable intracranial and extracranial disease for > 2 years. Further investigation may be warranted for high-dose trastuzumab for HER2-positive CNS metastases.