Breast-to-brain metastasis: A focus on the pre-metastatic niche

Abstract

Metastatic disease is the cause for 90% of breast cancer mortalities. For those 10%-20% of patients whose breast cancer metastasizes to the central nervous system, the one-year survival rate is just 20%. Both histology and molecular subtype have a correlation with the site of tumor metastasis, indicating an inherent preferential aspect to metastatic colony formation. The molecular differences between breast cancers may determine the site of metastasis through priming of the premetastatic niche in that site: cell surface molecules, exosomes released from the primary tumor, and soluble factors secreted from both the primary tumor and resident cells within the premetastatic niche all contribute to altering the premetastatic niche to be more favorable for the circulating tumor cells, allowing for cell invasion and growth. Here, we review breast to brain metastasis with a focus on the premetastatic niche. We discuss the secreted factors and exosomes that prime the premetastatic niche within the brain by instigating crosstalk between the resident cells of the brain microenvironment. We report on the individual roles that microglia, astrocytes, pericytes, neurons, and endothelial cells may have in the formation and maintenance of the premetastatic niche.