Primary systemic treatment of HER2-positive metastatic brain disease: profaning the sanctuary

The incorporation of anti-HER2 therapies has significantly altered the natural history of HER2-positive breast cancer, converting them from an aggressive tumor subtype to one with improved prognostic outcome (1). However, at the same time, it has been reported an apparent increase in the incidence of central nervous system (CNS) metastases, that can be explained by several factors including; (I) an intrinsinc biological predisposition of HER2-positive tumors to metastasize to CNS (2), (II) the extended survival of patients receiving trastuzumab that may actually heighten the risk of brain metastasis (3,4), and (III) the fact that trastuzumab does not penetrate well the bood-brain barrier (BBB), leading CNS to behaves as a sanctuary site (5).