Postoperative wound microenvironment regulates breast cancer stem cell fate and clinical implications.

The postoperative wound healing microenvironment in breast cancer is increasingly recognized as an active regulator of residual tumor cell behavior. Experimental evidence suggests that postoperative wound fluid, as a partial surrogate of the tumor bed, contains inflammatory cytokines and growth factors that can induce CSC-like phenotypes, self-renewal, and epithelial-mesenchymal transition in experimental models. These biological programs are associated with recurrence, metastasis, and treatment resistance. The biological effects of postoperative wound fluid are influenced by tumor characteristics and local treatments, particularly intraoperative radiotherapy, which can modulate its molecular composition and functional impact. Mechanistically, multiple signaling pathways, including inflammation-related networks and the JAK/STAT axis, appear to cooperatively regulate CSC fate within this dynamic niche. Postoperative wound fluid shows potential as a source of accessible biomarkers for monitoring local immune status and predicting clinical outcomes. However, current evidence is largely derived from simplified in vitro models and surrogate samples, limiting direct insights into the spatial and temporal complexity of the postoperative tumor bed. Future research integrating spatial multi-omics, advanced 3D models, and perioperative window interventions may enable precise characterization and targeted modulation of this microenvironment, providing opportunities for improving breast cancer outcomes.