Limitations in the Application of Clinicopathologic Factors Alone in Predicting Radiation Benefit for Women With Low-Risk Ductal Carcinoma In Situ After Breast Conserving Surgery: The Impact of a 7-Gene Biosignature Based on 10-Year Ipsilateral Breast Recurrence Rates

• Published in: International journal of radiation oncology, biology, physics
• Main Authors: Vicini, Frank, Shah, Chirag, Mittal, Karuna, Weinmann, Sheila, Leo, Michael, Mann, G. Bruce, Warnberg, Fredrik, Rabinovitch, Rachel, Czerniecki, Brian, Meattini, Icro, Khan, Atif Jalees, Jhawar, Sachin, Gerber, Naamit, Willey, Shawna C., Borgen, Pat, AlHilli, Zahraa, Kruse, Megan, Dabbs, David, Shivers, Steven C., Daily, Anna, Whitworth, Pat, Alvarado, Michael, Mouabbi, Jason A., Moran, Meena, Rugo, Hope, O’Shaughnessy, Joyce A., Bremer, Troy
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.07.2025
• ISSN: 0360-3016; 1879-355X; 1879-355X
• DOI: 10.1016/j.ijrobp.2025.07.1411

Clinicopathologic (CP) factors are used to estimate 10-year ipsilateral breast recurrence (IBR) risk and inform shared decision making regarding postoperative radiation therapy (RT) for ductal carcinoma in situ (DCIS) patients. This study assesses the clinical value of the 7-gene biosignature (DCISionRT) compared to traditional CP definitions for predicting IBR rates and RT benefit. DCIS patients (n = 926) treated with breast conserving surgery (BCS) ± RT were categorized as CP low-risk or high-risk based on established CP factors, study criteria, and nomograms. Women were classified as molecular Low Risk or High Risk by the biosignature. Ten-year IBR rates for CP risk groups were compared with and stratified by the biosignature. There were 37% of women classified as molecular Low Risk by the biosignature, an average of 47% were classified as low-risk by various CP definitions (range, 35% to 60%). Overall, CP low-risk groups had a mean absolute IBR benefit with RT of 6% (hazard ratio, 0.46; P < .001). The biosignature reclassified 53% of CP low-risk patients to molecular High rRisk. These reclassified patients experienced higher IBR rates when RT was omitted and benefited from RT (hazard ratio, 0.30; P < .001) with an absolute reduction of 11.6% (17.7% vs 6.1%). CP low-risk patients with concordant biosignature Low Risk demonstrated no significant RT benefit. On average, 28% of high-risk CP patients were reclassified as biosignature Low Risk and had no significant RT benefit (5.9% vs 4.0%). This observational study supports optimizing de-escalation/escalation treatment strategies for DCIS, the 7-gene biosignature reliably discriminating a LowRisk group without significant RT benefit compared with CP factors alone and a High Risk group that benefited from RT, facilitating improved shared decision making. A randomized clinical trial (NRG CC-016) will provide level 1A evidence for the impact of RT treatment on IBR rates for patients in the 7-gene biosignature Low Risk group, including those with CP high risk.