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Malone et al. J Cancer Metastasis Treat 2021;7:40 Journal of Cancer
DOI: 10.20517/2394-4722.2021.37
Metastasis and Treatment

Review Open Access

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

Kathryn Malone, Stella E. Tsirka

Department of Pharmacological Sciences, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY 11794-
8651, USA.
Correspondence to: Dr. Stella E. Tsirka, Department of Pharmacological Sciences, Renaissance School of Medicine at Stony
Brook University, Stony Brook, NY 11794-8651, USA. E-mail: styliani-anna.tsirka@stonybrook.edu
How to cite this article: Malone K, Tsirka SE. Breast-to-brain metastasis: a focus on the pre-metastatic niche. J Cancer Metastasis
Treat 2021;7:40. https://dx.doi.org/10.20517/2394-4722.2021.37
Received: 7 Feb 2021 First Decision: 12 Mar 2021 Revised: 5 Apr 2021 Accepted: 19 May 2021 First online: 24 May 2021

Academic Editors: Lombardi Giuseppe, Lucio Miele Copy Editor: Xi-Jun Chen Production Editor: Xi-Jun Chen

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.

Keywords: Niche, metastasis, breast cancer, brain

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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