Systemic treatment of brain metastases in HER2-positive breast cancer: current status and future directions

In recent years, brain metastases have emerged as a main challenge affecting the morbidity and mortality of patients with HER2-positive metastatic breast cancer. In the era following trastuzumab, approximately 30% of these patients develop brain metastases. Trastuzumab does not cross the blood-brain barrier, hence its role is limited to controlling extra-CNS metastases. Lapatinib emerged as a potential candidate; however, its use as a single agent was associated with modest responses. Combination with capecitabine was associated with good results, particularly in patients with newly diagnosed brain metastases. In this article, we discuss the role of trastuzumab and lapatinib in patients with HER2-positive breast cancer with brain metastases. We also highlight the complex structure of the blood-brain barrier and elucidate different potential strategies that could be useful in improving drug delivery.