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A Tri-Phasic View of the Microenvironment in Breast Cancer Brain Metastasis
Review Article  ·  Published: 27 September 2026
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Oncology Communications
Volume 1, Issue 2, 2026: 108-123
Review Article Open Access

A Tri-Phasic View of the Microenvironment in Breast Cancer Brain Metastasis

by
Ziqing Yuan Ziqing Yuan 1,2
Yanqing Wu Yanqing Wu 1
Yue Zhao Yue Zhao 1
Anli Yang Anli Yang 3 ORCID
Yuanhui Lai Yuanhui Lai 1 *
Weikai Xiao Weikai Xiao 1 * ORCID
1 Department of Thyroid and Breast Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou 510317, China
2 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510060, China
3 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
* Corresponding Authors: Yuanhui Lai, [email protected]; Weikai Xiao, [email protected]
Volume 1, Issue 2
Volume 1, Issue 2 2026
Received: 28 March 2026 Revised: 02 September 2026 Accepted: 23 September 2026 Published: 27 September 2026 CrossMark
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DOI: 10.62762/OC.2026.145571
ARK: ark:/57805/oc.2026.145571
You have full access to this open access article · CC BY 4.0 License

Article Information

Published in Oncology Communications
Volume/Issue Volume 1, Issue 2, 2026
Pages 108-123

Abstract

Breast cancer brain metastasis (BCBM) is driven by microenvironmental remodeling across three interconnected phases: the primary tumor microenvironment (TME) licenses dissemination, the pre-metastatic niche (PMN) primes the brain, and the established metastatic niche sustains outgrowth through central nervous system (CNS)-resident cell interactions. These phases are individually established; we integrate them through cross-phase signaling axes, exemplified by the proposed IL-6$\rightarrow$extracellular vesicle (EV)$\rightarrow$blood-brain barrier (BBB) disruption cascade, that link tumor-associated macrophage-driven epithelial-mesenchymal transition to PMN conditioning and niche maintenance. We integrate single-cell and spatial transcriptomic insights, discuss brain-specific mechanisms including astrocytic STAT3/connexin 43 signaling, neuronal contributions, and the neurovascular unit, and evaluate emerging therapies with emphasis on antibody-drug conjugates with intracranial activity. Subtype-specific differences between HER2-positive and triple-negative breast cancer brain metastases and key translational barriers are systematically addressed.

Graphical Abstract

A Tri-Phasic View of the Microenvironment in Breast Cancer Brain Metastasis

Keywords

Breast cancer brain metastasis Tumor microenvironment Pre-metastatic niche Metastatic niche Blood-brain barrier

Data Availability Statement

Not applicable.

Funding

This work was supported by the Natural Science Foundation of Guangdong Province, China under Grant 2026A1515012622.

Conflicts of Interest

The authors declare no conflicts of interest.

AI Use Statement

The authors declare that DeepSeek-V4-Pro was used for language editing and grammar refinement of the manuscript. The authors have carefully reviewed, revised, and verified the AI-assisted output and take full responsibility for the content of the manuscript.

Ethical Approval and Consent to Participate

Not applicable.

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APA Style
Yuan, Z., Wu, Y., Zhao, Y., Yang, A., Lai, Y., & Xiao, W. (2026). A Tri-Phasic View of the Microenvironment in Breast Cancer Brain Metastasis. Oncology Communications, 1(2), 108-123. https://doi.org/10.62762/OC.2026.145571
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TY  - JOUR
AU  - Yuan, Ziqing
AU  - Wu, Yanqing
AU  - Zhao, Yue
AU  - Yang, Anli
AU  - Lai, Yuanhui
AU  - Xiao, Weikai
PY  - 2026
DA  - 2026/09/27
TI  - A Tri-Phasic View of the Microenvironment in Breast Cancer Brain Metastasis
JO  - Oncology Communications
T2  - Oncology Communications
JF  - Oncology Communications
VL  - 1
IS  - 2
SP  - 108
EP  - 123
DO  - 10.62762/OC.2026.145571
UR  - https://www.icck.org/article/abs/OC.2026.145571
KW  - Breast cancer brain metastasis
KW  - Tumor microenvironment
KW  - Pre-metastatic niche
KW  - Metastatic niche
KW  - Blood-brain barrier
AB  - Breast cancer brain metastasis (BCBM) is driven by microenvironmental remodeling across three interconnected phases: the primary tumor microenvironment (TME) licenses dissemination, the pre-metastatic niche (PMN) primes the brain, and the established metastatic niche sustains outgrowth through central nervous system (CNS)-resident cell interactions. These phases are individually established; we integrate them through cross-phase signaling axes, exemplified by the proposed IL-6$\rightarrow$extracellular vesicle (EV)$\rightarrow$blood-brain barrier (BBB) disruption cascade, that link tumor-associated macrophage-driven epithelial-mesenchymal transition to PMN conditioning and niche maintenance. We integrate single-cell and spatial transcriptomic insights, discuss brain-specific mechanisms including astrocytic STAT3/connexin 43 signaling, neuronal contributions, and the neurovascular unit, and evaluate emerging therapies with emphasis on antibody-drug conjugates with intracranial activity. Subtype-specific differences between HER2-positive and triple-negative breast cancer brain metastases and key translational barriers are systematically addressed.
SN  - 3142-8894
PB  - Institute of Central Computation and Knowledge
LA  - English
ER  -
BibTeX Format
Compatible with LaTeX, BibTeX, and other reference managers
@article{Yuan2026A,
  author = {Ziqing Yuan and Yanqing Wu and Yue Zhao and Anli Yang and Yuanhui Lai and Weikai Xiao},
  title = {A Tri-Phasic View of the Microenvironment in Breast Cancer Brain Metastasis},
  journal = {Oncology Communications},
  year = {2026},
  volume = {1},
  number = {2},
  pages = {108-123},
  doi = {10.62762/OC.2026.145571},
  url = {https://www.icck.org/article/abs/OC.2026.145571},
  abstract = {Breast cancer brain metastasis (BCBM) is driven by microenvironmental remodeling across three interconnected phases: the primary tumor microenvironment (TME) licenses dissemination, the pre-metastatic niche (PMN) primes the brain, and the established metastatic niche sustains outgrowth through central nervous system (CNS)-resident cell interactions. These phases are individually established; we integrate them through cross-phase signaling axes, exemplified by the proposed IL-6\$\rightarrow\$extracellular vesicle (EV)\$\rightarrow\$blood-brain barrier (BBB) disruption cascade, that link tumor-associated macrophage-driven epithelial-mesenchymal transition to PMN conditioning and niche maintenance. We integrate single-cell and spatial transcriptomic insights, discuss brain-specific mechanisms including astrocytic STAT3/connexin 43 signaling, neuronal contributions, and the neurovascular unit, and evaluate emerging therapies with emphasis on antibody-drug conjugates with intracranial activity. Subtype-specific differences between HER2-positive and triple-negative breast cancer brain metastases and key translational barriers are systematically addressed.},
  keywords = {Breast cancer brain metastasis, Tumor microenvironment, Pre-metastatic niche, Metastatic niche, Blood-brain barrier},
  issn = {3142-8894},
  publisher = {Institute of Central Computation and Knowledge}
}

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CC BY Copyright © 2026 by the Author(s). Published by Institute of Central Computation and Knowledge. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
Oncology Communications
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