Targeting brain metastases in breast cancer

Brain metastases (BMs) ar e an important source of morbidity and mortality in patients with metastatic breast cancer (BC). As survival of patients with advanced BC considerably improved thanks to research advancements and new therapeutic approaches, the apparent incidence of BMs is increasing. Local interventions, in the form of either surgical resection or radiation therapy, remain the mainstay in the management of BMs. Systemic treat-ments are typically used to complement local strategies to further improve and maintain control of central nervous system (CNS) disease. Although high-level evidence data about the impact of the blood-brain barrier (BBB), as wel l as the efficacy of anti-cancer agents on BMs and differentials between the systemic compartment and CNS are sti l l scant, our understanding of the activity of systemic treatments with impact on BMs is rapidly evolving. Novel anti-HER2 agents, such as tucatinib, ado-trastuzumab emtansine, trastuzumab deruxtecan and neratinib, have shown intracranial efficacy. Current research efforts are ongoing not only to clari f y the activity of existing treatments on the CNS, as wel l as to develop new drugs and innovative multi-modality approaches.This review w i l l encompass the current treatment landscape of BMs arising from BC, with a focus on recent advancements in the field and investigational approaches.