Abstract PS5-08-26: The PREDICT II Registry: A Prospective Study to Evaluate the Clinical Utility of a 7-Gene Predictive Biosignature on Treatment Decisions in Patients with Ductal Carcinoma In Situ

Abstract Purpose/Objective(s): A majority of women with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) do not benefit from adjuvant radiation therapy (RT). However, evidence from randomized clinical trials supports the role of RT in reducing the risk of local recurrence. Given the understanding that more than two-thirds of women with DCIS do not recur after BCS alone, NCCN guidelines recommend utilization of RTOG-9804 criteria (screening detected, grade I/II, size ≤ 2.5 cm, margins ≥ 3 mm) to consider omitting RT after BCS for DCIS. To overcome limitations of clfinicopathologic (CP) risk assessment, a validated biosignature that integrates the protein expression of seven genes and four CP factors (DCISionRT, PreludeDx, Laguna Hills, CA) is currently in use in many breast centers. The 7-gene biosignature has been clinically validated to be both prognostic for in breast recurrence (IBR) risk and predictive for response to RT. Recent evidence demonstrates that approximately half of patients meeting RTOG-9804-like critera wil be identified by the 7-gene biosignature as having elevated IBR risk and significant RT benefit. The study assesses factors impacting shared decision-making, including physician recommendations and patient preferences incorporating the biosignature test results along with CP factors. The main outcome is the impact of test results on individual preferences and treatment recommendations. Materials/Methods: PREDICT II is a multicenter (30 site), prospective, observational registry, open to 3000 women with DCIS. Primary endpoints are changes in treatment recommendations for surgery, RT, and hormonal therapy. Secondary endpoints are identification of key drivers for treatment recommendations, such as age, size, grade, patient preference, biosignature status and IBR risk. The study is open to females age 30-85 who are candidates for BCS and eligible for RT and/or systemic treatment. Subjects must not have been previously treated for DCIS or invasive breast cancer. DCIS patients, breast surgeons, and radiation oncologist participate in informed, shared, decision-making based on standard CP criteria. The preference and strength of preference for mastectomy vs. breast conservation (BCS) and radiation treatment (RT) vs. no RT, following shared decision-making, is recorded before and after biosignature results are available. Recurrence rates at 5 and 10 years will be documented. Changes in treatment recommendations will be analyzed using McNemar's test (alpha level = 0.05). Multivariable logistic regression will be used to determine odds ratios of CP factors affecting pre- and post-test treatment recommendations. Covariates include hormone receptor status, nuclear grade, tumor necrosis, family history of breast cancer, race, ethnicity, patient preference, physician specialty, and the biosignature score. Differences in recurrence-free and overall survival will be assessed by Kaplan-Meier survival analysis using the log-rank test and/or the Cox Proportional Hazards model. The study has been approved by WCG IRB (Tracking #20172841) and/or local IRBs at each site. ClinicalTrials.gov: NCT03448926. Citation Format: P. Borgen, P. Whitworth, A. Daily, K. Mittal, S. Shivers, T. Bremer. The PREDICT II Registry: A Prospective Study to Evaluate the Clinical Utility of a 7-Gene Predictive Biosignature on Treatment Decisions in Patients with Ductal Carcinoma In Situ [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-08-26.