Central nervous system (CNS)
metastases from
breast cancer (BC) represent an important cause of disease-related morbidity and mortality. For BC patients who develop CNS
metastases, local control measures (both surgery and radiation) are essentially palliative and usually poorly effective, with systemic
therapies often failing to achieve optimal control mainly due to the presence of the blood-brain barrier which hampers adequate penetration of therapeutic agents into the brain. However, recent evidence suggests that the status of the human
epidermal growth factor receptor-2 (HER2) strongly influences the incidence of CNS
metastases and the survival of BC patients from the time of development of CNS
metastases, with HER2-positive (HER2+) patients generally experiencing higher rates of CNS
metastases and prolonged overall survival compared to patients with HER2-negative disease. This phenomenon likely reflects the difficult CNS
drug-penetration and improved control of extra-
CNS disease following the clinical use of the anti-HER2
monoclonal antibody trastuzumab. Importantly, this HER2-based survival difference has important implications when planning the optimal treatment of BC patients with CNS
metastases. To date, although no systemic
therapy has been specifically approved for the treatment of CNS
metastases from BC, several targeted agents are being clinically developed for this purpose. In the present review we will discuss the targeted
therapies that are under investigation for the treatment of CNS
metastases from BC, highlighting the different implications based on whether a given agent is being developed to target CNS
metastases from HER2+ or HER2-negative
breast cancer.