Therapeutic strategies for HER2-positive breast cancer with central nervous system involvement: a literature review and future perspectives

Background and Objective: Brain metastases (BMs) are present in approximately 55% of patients with HER2-positive breast cancer (HER2+ BC). The introduction of anti-HER2 agents has radically changed the prognosis of these tumors, prolonging the overall survival of these patients. 'Methods: In this review, we describe the biology of central nervous system (CNS) spreading in patients with HER2+ BC. We also provide a literature review of current treatment strategies of brain metastatic BC, focusing on HER2+ disease, and future perspectives.Key Content and Findings: Treatment of symptomatic BMs includes traditionally neurosurgery and/or radiotherapy, depending on the number of metastases, performance status and systemic control disease. Local treatments, such as surgical excision of BM and stereotactic radiosurgery (SRS), when feasible, are preferred over whole-brain radiotherapy, because of related cognitive impairment. These treatments can lead to a local control of the disease, however, systemic relapses can affect the prognosis of these patients. Recently, new anti-HER2 agents have demonstrated to be effective on BMs, thereby leading to improved survival outcomes in this setting, with an acceptable quality of life. Despite the clinical benefit of these approaches, BMs still represent a cause of death and effective therapeutic strategies are needed.Conclusions: Different targeted agents have demonstrated significant efficacy with tolerable safety profiles in HER2+ BC patients with BM, and have already been approved for clinical use in this setting. A better understanding of the molecular mechanisms underlying the onset of BMs could suggest novel targeted agents in order to prevent CNS localization ore delay progression to CNS in HER-2 metastatic patients.