Abstract

A higher propensity of developing brain metastasis exists in triple-negative breast cancer (TNBC). Upon comparing the metastatic patterns of all breast cancer subtypes, patients with TNBC exhibited increased risks of the brain being the initial metastatic site, early brain metastasis development, and shortest brain metastasis-related survival. Notably, the development of brain metastasis differs from that at other sites owing to the brain-unique microvasculature (blood brain barrier (BBB)) and intracerebral microenvironment. Studies of brain metastases from TNBC have revealed the poorest treatment response, mostly because of the relatively backward strategies to target vast disease heterogeneity and poor brain efficacy. Moreover, TNBC is highly associated with the existence of cancer stem cells (CSCs), which contribute to circulating cancer cell survival before BBB extravasation, evasion from immune surveillance, and plasticity in adaptation to the brain-specific microenvironment. We summarized recent literature regarding molecules and pathways and reviewed the effects of CSC biology during the formation of brain metastasis in TNBC. Along with the concept of individualized cancer therapy, certain strategies, namely the patient-derived xenograft model to overcome the lack of treatment-relevant TNBC classification and techniques in BBB disruption to enhance brain efficacy has been proposed in the hope of achieving treatment success.

Highlights

  • After lung cancer, breast cancer is the second most frequently diagnosed origin of brain metastases [1]

  • We summarized current clinical practices and trials on patients with BM-triple-negative breast cancer (TNBC), whereas multiple mechanisms underlying cancer stem cells (CSCs) biology alongside brain metastatic tumorigenesis were reviewed systemically, namely epithelial–mesenchymal transition (EMT), autophagy, immune evasion, niches, dormancy, proliferation, and tumorigenesis

  • The principle of choosing the chemotherapy regimen for brain metastasis largely depends on the active agents against primaries

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Summary

Introduction

Breast cancer is the second most frequently diagnosed origin of brain metastases [1]. Cancers 2020, 12, 2122 brain barrier (BBB) penetrance, the actual and reported incidence of brain metastases in breast cancer is likely to increase. Risk factors for brain metastasis include age

Triple-Negative Breast Cancer and Brain Metastasis
Current Treatment Practices and Challenges in BM-TNBC
Loco-Regional Treatment
Systemic Therapy
Current Clinical Trials in BM-TNBC
Immune Checkpoint Molecule Inhibitor
Anti-Angiogenic Agent
Brain-Penetrating Peptide Drug Conjugate
Effects of CSC Biology on BM-TNBC
Extravasation from the BBB
Dormant Period of CSCs Adaptation to the Brain Microenvironment
Patient Derived Xenograft Model: A Solution to the Diverse TNBC Heterogeneity
Techniques in Opening BBB or Blood-Tumor Barriers
Bypassing the BBB and BTB
Findings
Conclusions

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