Margin of Error: The Emerging Role of Field Cancerization in Predicting Recurrence Risk of Ductal Carcinoma In Situ

Although ductal carcinoma in situ (DCIS) diagnoses continue to climb, patient management remains constrained by limitations in recurrence prediction. Conventional histopathology and existing prognostic parameters often inadequately predict local recurrence, leading to over- or under-treatment. Additionally, discourse remains over the clinical implications of margin width as a measure of recurrence risk, demonstrating the limitations of a margin-based model, and motivating our proposal that recurrence risk is dynamic and should be defined by patient-specific, spatially resolved diagnostic biomarkers. This review introduces field cancerization as a framework that may illuminate mechanisms underlying DCIS ipsilateral recurrence and improve clinical decision-making. We propose that the potential drivers of ductal field cancerization span two stages: pre-tumorigenesis and post-tumorigenesis. Pre-tumorigenic events include non-biological and biological exposome factors. Post-tumorigenic drivers include intratumoral and microenvironment-mediated remodeling of adjacent tissues that promote malignancy. This review bridges stage-specific molecular mechanisms to potentially actionable strategies for DCIS patient management-particularly margin assessment and recurrence risk prognostication-while highlighting the critical unmet need to identify biomarkers that measure high-risk field changes. We also emphasize the need to move beyond lesion-centric management toward multivariable prognostic models that include distance-mapped field biomarkers, enabling more precise surgery, improved selection of adjuvant therapy, and safer de-escalation for low-risk patients.