Targeting the tumor microenvironment: a new strategy for natural products in breast cancer therapy.

The development and drug resistance of breast cancer are closely associated with the heterogeneity of the tumor microenvironment (TME). Immunosuppressive cells, activated matrix components, abnormal vascular networks, and metabolic reprogramming within the TME collectively create a niche that promotes tumor survival. Despite the clinical adoption of emerging therapies such as immune checkpoint inhibitors, overall response rates remain constrained by the suppressive characteristics of the TME. Natural products, with their multi-component, multi-targeted, and low-toxicity advantages, demonstrate significant potential in reshaping the TME. This systematic review summarizes recent advances in natural products regulating the breast cancer TME. We highlight the molecular mechanisms by which natural products reverse immunosuppression, normalize tumor vasculature, inhibit stromal fibrosis, and correct metabolic dysregulation. Additionally, synergistic strategies combining natural products with chemotherapy and immunotherapy are explored, particularly how nanotechnology-based delivery systems overcome pharmacokinetic barriers. Finally, we critically analyze translational challenges in this field and outline future research directions.