Chronic Radiation Dermatitis After Breast Cancer Radiotherapy: Mechanistic Insights, Therapeutic Challenges, and Emerging Roles of Piezo1-Mediated Mechanotransduction.

Background: Chronic radiation dermatitis (CRD) is a common late complication of postoperative radiotherapy for breast cancer. Its pathological process involves multiple interrelated factors, including persistent inflammation, microvascular injury, fibrosis, and tissue remodeling, and may substantially impair patients' quality of life. Current clinical management remains largely symptomatic, including topical therapies, hyperbaric oxygen therapy, laser treatment, and fat grafting; however, overall therapeutic efficacy remains limited, suggesting that the underlying mechanisms of CRD have not yet been fully elucidated. Objective: This review aims to integrate the major pathological mechanisms underlying CRD after breast cancer surgery and the limitations of current therapeutic strategies, and to propose a mechanistic explanatory framework from the perspective of mechanotransduction, with the goal of exploring potential reasons for the limited efficacy of existing treatments. Methods: By reviewing the relevant literature, this article systematically integrates key pathological processes involved in CRD, including inflammatory responses, vascular dysfunction, and fibrotic remodeling, and further interprets these processes in light of recent advances in the mechanical microenvironment and mechanotransduction. Results: Current evidence indicates that the development and progression of CRD are closely associated with persistent inflammation, microvascular injury, and progressive fibrosis. However, alterations in the mechanical microenvironment caused by extracellular matrix deposition and increased tissue stiffness after radiation injury may represent an important but underrecognized regulatory factor. Multiple mechanotransduction pathways may be involved in this process, including integrin-mediated adhesion signaling, the YAP/TAZ pathway, and transient receptor potential channels. As a representative mechanosensitive ion channel, Piezo1 has been implicated in the regulation of inflammation, vascular function, and fibrosis-related processes. Nevertheless, direct evidence regarding its role in CRD remains limited, and current assumptions are largely extrapolated from indirect findings in other tissues or disease models. Conclusion: This review re-examines the pathological process of CRD from the perspective of the mechanical microenvironment and its associated mechanotransduction mechanisms, positioning Piezo1 as a potential mechanistic link rather than a proven central pathogenic driver. This perspective may help contextualize the development and progression of CRD within a broader mechanotransduction network and provide a hypothesis-generating basis for future mechanistic studies and potential targeted interventions.