A scalable outpatient framework for BI-RADS 2-4B breast nodule management: an iodine-DMSO transdermal protocol

Low- to intermediate-suspicion breast nodules (BI-RADS 2-4B) generate diagnostic uncertainty, prolonged surveillance, and emotional and operational burden, often without established low-risk interventions designed to support short-interval physiological modulation. Given the redox, endocrine, vascular, and microenvironmental dependencies of benign breast lesions, physiology-guided outpatient modulation may contribute to response-oriented decision-making before conventional oncologic escalation.

A structured translational outpatient protocol was developed through mechanistic evidence synthesis, multicriteria translational prioritization, protocol structuring, and exploratory clinical implementation. The workflow integrated Evidence-Informed Design, Work Breakdown Structure, multicriteria decision analysis (MCDA), and DesignThinking/Open Innovation. Systematic reviews of molecular iodine and dimethyl sulfoxide (DMSO) identified translational response domains and mechanistic convergence pathways associated with tissue accessibility, redox modulation, and outpatient feasibility.

The translational synthesis identified redox modulation, vascular responsiveness, microenvironmental stabilization, tissue accessibility, and immune-related physiological modulation as principal mechanistic domains associated with iodine-responsive breast-tissue modulation. Comparative prioritization identified the transdermal route as the most operationally feasible outpatient configuration. The finalized protocol-2.5 mL of Lugol's solution (5% iodine) combined with 2.5 mL of pharmaceutical-grade DMSO (99.9%), applied transdermally twice weekly for five weeks-was implemented in three exploratory BI-RADS 4B cases using short-interval MRI and ultrasound reassessment. Two cases demonstrated complete radiologic resolution accompanied by vascular-signal normalization and stromal remodeling, including simultaneous remodeling of contralateral BI-RADS 2 nodules; one remained lesion-free during 12-month follow-up. A third case demonstrated a partial imaging-response pattern and was referred for fine-needle aspiration according to predefined reassessment criteria. No major adverse effects or tolerability-related discontinuations occurred; the intervention was discontinued after six sessions in the third case according to the predefined imaging-based stopping rule.

The framework integrates physiological modulation with response-oriented imaging reassessment while preserving compatibility with conventional oncologic workflows. Its low-complexity and reproducible outpatient architecture may possess translational relevance within resource-sensitive and Value-Based Healthcare-oriented breast-care settings.

The exploratory implementation of the iodine-DMSO transdermal protocol yielded biologically coherent, imaging-detectable, and operationally reproducible response patterns compatible with short-interval physiological modulation. These findings support controlled outpatient and implementation-oriented investigations evaluating reproducibility, scalability, cost impact, and broader translational applicability.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251122511, PROSPERO CRD420251122511; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251123805, PROSPERO CRD420251123805.