Abstract 7477: Conquering overtreatment of ductal carcinoma in situ through integrative team science

Abstract Ductal carcinoma in situ (DCIS), often misclassified as early-stage breast cancer, rarely progresses to invasive disease. Yet, the inability to distinguish between indolent and aggressive DCIS leads to widespread overtreatment, burdening thousands of women globally. Addressing this, the PRECISION team, under the Cancer Grand Challenges initiative, has achieved remarkable advancements, driving a paradigm shift in DCIS management. PRECISION exemplifies next-level team science, merging expertise from 10 institutions across the USA, UK, and the Netherlands. Spanning disciplines such as epidemiology, molecular biology, AI, pathology, clinical expertise, health outcomes, and patient advocacy, the team’s interdisciplinary approach enabled transformative breakthroughs. Key achievements include: 1. Understanding DCIS Biology: Using innovative patient-derived DCIS-MIND models and single-cell genomic techniques, PRECISION revealed that genetic changes alone do not dictate progression. These findings challenge long-held assumptions, emphasizing the need for comprehensive approaches to assess risk. 2. Risk Stratification Methodologies: Novel biomarkers, AI-driven morphometric analyses, and an RNA-seq classifier reliably differentiate high-risk from low-risk DCIS. For example, the RNA-seq classifier identified low-risk DCIS with a 98% negative predictive value, paving the way for treatment de-escalation. 3. Testing Active Surveillance: Clinical trials embedded in PRECISION’ (COMET, LORD, LORIS) explored the safety of active surveillance, potentially replacing invasive treatments for low-risk DCIS with cost-effective outcomes. Patient engagement and shared decision-making tools further enhance personalized care strategies. PRECISION’s success stems from dynamic international collaborations and integration of advanced technologies. Its findings not only redefine DCIS management but also establish a blueprint for addressing other low-risk malignancies. By focusing on biology-based, patient-centered solutions, PRECISION ensures that treatment aligns with the true nature of the disease, paving the path to transform DCIS care worldwide. To do so, the team aims to develop dynamic risk forecasting techniques, powered by evolutionary AI, drawing inspiration from geoscience methodologies. The team also plans to establish a Global Virtual DCIS Monitoring Clinic, enabling worldwide participation. This initiative will support personalized care, foster shared decision-making, and minimize clinic visits through standardized data collection and seamless online follow-ups. Citation Format: Jelle Wesseling, Proteeti Bhattacharjee, Esther H. Lips, Elinor J. Sawyer, E. Shelley Hwang, Alastair M. Thompson, Grand Challenge PRECISION Consortium. Conquering overtreatment of ductal carcinoma in situ through integrative team science [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7477.