Molecular aspects of brain metastases in breast cancer

• Published in: Cancer treatment reviews 2023-03, Vol.114, p.102521-102521, Article 102521
• Main Authors: Tomasik, Bartłomiej, Bieńkowski, Michał, Górska, Zuzanna, Gutowska, Klaudia, Kumięga, Paulina, Jassem, Jacek, Duchnowska, Renata
• Format: Article
• Language: English
• Subjects: Biomarkers; Brain metastases; Brain microenvironment, biomarkers; Brain Neoplasms - secondary; Breast cancer; Breast Neoplasms - pathology; Female; Humans; Triple Negative Breast Neoplasms - pathology; Tumor Microenvironment
• ISSN: 0305-7372; 1532-1967
• DOI: 10.1016/j.ctrv.2023.102521

•Breast cancer is one of the most frequent causes of brain metastases.•Subtype switching is a common phenomenon that may occur in up to one-third of patients with breast cancer brain metastases.•Breast cancer cells can modify the brain extracellular matrix to create a metastatic niche.•Several genetic factors are responsible for breast cancer cells’ brain tropism.•Novel, less invasive circulating biomarkers may help predict of brain metastases from breast cancer. Brain metastases (BM) are a common and devastating manifestation of breast cancer (BC). BM are particularly frequent in the HER2-positive and triple-negative breast cancer phenotypes and usually occur following the metastatic spread to extracranial sites. Several genes mediating BM and biomarkers predicting their risk in BC have been reported in the past decade. These findings have advanced the understanding of BM pathobiology and paved the way for developing new therapeutic strategies but they still warrant a thorough clinical validation. Hence, a better understanding of the mechanistic aspects of BM and delineating the interactions of tumor cells with the brain microenvironment are of utmost importance. This review discusses the molecular basis of the metastatic cascade: the epithelial-mesenchymal transition, cancer, and tumor microenvironment interaction and intravasation, priming of the metastatic niche in the brain, and survival in the new site. We also outline the postulated mechanisms of BC cells’ brain tropism. Finally, we discuss advances in the field of biomarkers (both tissue-based and liquid-based) that predict BM from BC.