Prevention of brain metastases in human epidermal growth factor receptor 2-positive breast cancer

For patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, treatments that could prevent or delay occurrence of brain metastases would improve outcome.

Few studies were specifically designed to assess brain metastasis prevention. Most evidence derives from subgroup analyses of randomized trials. In the first-line metastatic setting, lapatinib, was not superior to trastuzumab to prevent CNS metastases as first site of relapse. Pertuzumab when added to trastuzumab and taxane significantly delay occurrence of brain metastases. In the second line setting, trastuzumab-emtansine has shown to improve overall survival of patients with brain metastases when compared with capecitabine-lapatinib, but there was no significant delay in brain metastases progression. Neratinib, has shown that it was able to delay brain metastases progression. Finally, tucatinib, has demonstrated benefit in progression-free survival and overall survival in combination with trastuzumab and capecitabine over trastuzumab and capecitabine for patients with or without brain metastases.

There has been an impressive improvement of the outcome of patients with HER2-positive metastatic breast cancer, with improved control of systemic disease and delayed occurrence of CNS progression. Specific studies are needed to assess TKI for brain metastases prevention, particularly in the adjuvant setting.