title: Breast cancer brain metastases: biology and new clinical perspectives.
abstract: Because of improvements in the treatment of patients with metastatic breast cancer, the development of brain metastases (BM) has become a major limitation of life expectancy and quality of life for many breast cancer patients. The improvement of management strategies for BM is thus an important clinical challenge, especially among high-risk patients such as human epidermal growth factor receptor 2-positive and triple-negative patients. However, the formation of BM as a multistep process is thus far poorly understood. To grow in the brain, single tumor cells must pass through the tight blood-brain barrier (BBB). The BBB represents an obstacle for circulating tumor cells entering the brain, but it also plays a protective role against immune cell and toxic agents once metastatic cells have colonized the cerebral compartment. Furthermore, animal studies have shown that, after passing the BBB, the tumor cells not only require close contact with endothelial cells but also interact closely with many different brain residential cells. Thus, in addition to a genetic predisposition of the tumor cells, cellular adaptation processes within the new microenvironment may also determine the ability of a tumor cell to metastasize. In this review, we summarize the biology of breast cancer that has spread into the brain and discuss the implications for current and potential future treatment strategies.
authors.affiliation: Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany. iwitzel@uke.de.
authors.forename: Isabell
authors.initials: I
authors.lastname: Witzel
authors.affiliation: Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany. ferrer@uke.de.
authors.forename: Leticia
authors.initials: L
authors.lastname: Oliveira-Ferrer
authors.affiliation: Institute of Tumour Biology, University Medical Center Hamburg-Eppendorf, Center of Experimental Medicine, Martinistraße 52, 20246, Hamburg, Germany. pantel@uke.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.affiliation: Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany. v.mueller@uke.de.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Müller
authors.affiliation: Institute of Tumour Biology, University Medical Center Hamburg-Eppendorf, Center of Experimental Medicine, Martinistraße 52, 20246, Hamburg, Germany. h.wikman@uke.de.
authors.forename: Harriet
authors.initials: H
authors.lastname: Wikman
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D009362:Neoplasm Metastasis