REVIEW article
Front. Pharmacol.
Sec. Ethnopharmacology
TCM Herb Pairs Regulate Breast Cancer TME Heterogeneous Mechanisms in Immune, Vascular, and Stromal Compartments
- LL
Lu Liu
- YZ
Yuxuan Zhang
- JF
Jing Feng
- HY
Hua Yang
- CF
Chunling Fan
- XD
Xiaoxia Ding
- QM
Qiong Min
- XD
XiaoYan Dai
- XL
Xudong Lei
- WS
Wei Shen
Gansu Provincial Cancer Hospital, Lanzhou, China
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Abstract
Background: Breast cancer is the most prevalent malignancy in women, and its complex tumor microenvironment (TME) characterized by immunosuppression, aberrant angiogenesis and stromal fibrosis is a critical cause of therapeutic failure. Traditional Chinese Medicine (TCM) herb pairs, with multi-target, multi-component and multi-dimensional modes of action, show unique advantages in modulating the breast cancer TME. Core Findings: This study systematically reviewed the regulatory mechanisms of 20 core anti-breast cancer herb pairs on the TME. Heat-clearing and detoxifying herb pairs (e.g., Hedyotis diffusa-Scutellaria barbata) principally reshape the immune microenvironment by activating CD8⁺ T cells and promoting M2-to-M1 polarization of tumor-associated macrophages (TAMs). Blood-activating and stasis-resolving herb pairs (e.g., Sparganium stoloniferum-Curcuma zedoaria) inhibit tumor angiogenesis via targeting VEGF/VEGFR2 and ITGA5/CCN1 pathways. Qi-tonifying and pathogen-eliminating herb pairs (e.g., Astragalus membranaceus-Curcuma zedoaria) ameliorate stromal fibrosis by suppressing cancer-associated fibroblast (CAF) activation and modulating the TGF-β/Smad pathway. Conclusion: TCM herb pairs have substantial value in systematically remodeling the breast cancer TME and advancing integrative oncology. Nano-enabled delivery systems serve as a critical technical solution to overcome the intrinsic pharmacokinetic defects of herbal bioactive components and accelerate their clinical translation. The clinical translation pathway based on "syndrome differentiation-guided herb pair selection–precision TME modulation–synergistic efficacy enhancement" is expected to provide more precise, safe and effective therapeutic options for breast cancer patients.
Summary
Keywords
breast cancer, heterogeneity, Immune-vascular-stromal crosstalk, Traditional Chinese Medicine herb pair, Tumor Microenvironment
Received
11 May 2026
Accepted
13 July 2026
Copyright
© 2026 Liu, Zhang, Feng, Yang, Fan, Ding, Min, Dai, Lei and Shen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Lu Liu
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.