TCM herb pairs regulate breast cancer TME heterogeneous mechanisms in immune, vascular, and stromal compartments

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.

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-C. zedoaria) ameliorate stromal fibrosis by suppressing cancer-associated fibroblast (CAF) activation and modulating the TGF-β/Smad pathway.

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.