Treatment strategies for breast cancer brain metastases

Abstract

Brain metastases from breast cancer (BCBM) constitute the second most common cause of brain metastasis (BM), and the incidence of these frequently lethal lesions is currently increasing, following better systemic treatment. Patients with ER-negative and HER2-positive metastatic breast cancer (BC) are the most likely to develop BM, but if this diagnosis remains associated with a worse prognosis, long survival is now common for patients with HER2-positive BC. BCBM represents a therapeutic challenge that needs a coordinated treatment strategy along international guidelines. Surgery has always to be considered when feasible. It is now well established that stereotaxic radiosurgery allows for equivalent control and less-cognitive toxicities than whole-brain radiation therapy, which should be delayed as much as possible. Medical treatment for BCBM is currently a rapidly evolving field. It has been shown that the blood-brain barrier (BBB) is often impaired in macroscopic BM, and several chemotherapy regimens, antibody-drug conjugates and tyrosine-kinase inhibitors have been shown to be active on BCBM and can be part of the global treatment strategy. This paper provides an overview of the therapeutic option for BCBM that is currently available and outlines potential new approaches for tackling these deadly secondary tumours.

Fig. 1. BMBC history.

Following haematogenous dissemination, breast cancer cells invade the brain tissue by extravasation. Then they experience perivascular growth with no need of neoangiogenesis and the blood–brain barrier (BBB) is still intact. To reach macroscopic size, the new metastasis needs to stimulate neoangiogenesis. At this point, the BBB may be disrupted and is referred as the blood–tumour barrier (BTB). This Figure has been adapted from Eicher et al..

Fig. 2

Main blood–brain barrier (BBB) disrupting strategies under development: osmotic disruption, microbubble-assisted focused ultrasound (FUS) and nanoparticules conjugated with cancer agent.