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Understanding Patterns of Brain Metastasis in Triple-Negative Breast Cancer and Exploring Potential Therapeutic Targets

Authors Lv Y, Ma X, Du Y, Feng J

Received 24 November 2020

Accepted for publication 6 January 2021

Published 22 January 2021 Volume 2021:14 Pages 589—607


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Takuya Aoki

Yan Lv,1 Xiao Ma,2 Yuxin Du,1 Jifeng Feng1

1The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing 210009, People’s Republic of China; 2Department of General Surgery, The Affiliated Zhongda Hospital of Southeast University, Nanjing 210009, People’s Republic of China

Correspondence: Jifeng Feng
The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, 42 Baiziting, Nanjing 210009, People’s Republic of China
Tel/Fax +86 02583283584

Abstract: Triple-negative breast cancer (TNBC) is a highly malignant subtype of breast cancer. High invasiveness and heterogeneity, as well as a lack of drug targets, are the main factors leading to poor prognosis. Brain metastasis (BM) is a serious event threatening the life of breast cancer patients, especially those with TNBC. Compared with that for hormone receptor-positive and HER2-positive breast cancers, TNBC-derived BM (TNBCBM) occurs earlier and more frequently, and has a worse prognosis. There is no standard treatment for BM to date, and one is urgently required. In this review, we discuss the current knowledge regarding the developmental patterns of TNBCBM, focusing on the key events in BM formation. Specifically, we consider (i) the nature and function of TNBC cells; (ii) how TNBC cells cross the blood–brain barrier and form a fenestrated, more permeable blood–tumor barrier; (iii) the biological characteristics of TNBCBM; and (iv) the infiltration and colonization of the central nervous system (CNS) by TNBC cells, including the establishment of premetastatic niches, immunosurveillance escape, and metabolic adaptations. We also discuss putative therapeutic targets and precision therapy with the greatest potential to treat TNBCBM, and summarize the relevant completed and ongoing clinical trials. These findings may provide new insights into the prevention and treatment of BM in TNBC patients.

Keywords: triple-negative breast cancer, brain metastasis, blood–brain barrier, blood–tumor barrier, microenvironment, therapeutic targets

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