Prognostic Risk Assessment and Prediction of Radiotherapy Benefit for Women with Ductal Carcinoma In Situ (DCIS) of the Breast, in a Randomized Clinical Trial (SweDCIS)

SIMPLE SUMMARY: Despite clinical advancements in the diagnosis and treatment of DCIS, tailoring individual treatment for women diagnosed with DCIS remains an unmet clinical need. Definitive predictive tools that can predict who will or not benefit from radiation therapy (RT) after breast conserving surgery (BCS) remains elusive. Here, we used a prospective–retrospective design to validate DCISionRT(®), using data from the SweDCIS randomized clinical trial. DCISionRT identified women with elevated recurrence risk who benefited substantially from RT after BCS. In addition, the test identified women with low recurrence risk and little benefit from RT. These results support our conclusions that knowledge of the individual risk and benefit from RT provided by the test can help clinicians and patients make individualized treatment decisions for women diagnosed with DCIS. ABSTRACT: Prediction of radiotherapy (RT) benefit after breast-conserving surgery (BCS) for DCIS is crucial. The aim was to validate a biosignature, DCISionRT(®), in the SweDCIS randomized trial. Women were randomly assigned to RT or not after BCS, between 1987 and 2000. Tumor blocks were collected, and slides were sent to PreludeDx(TM) for testing. In 504 women with complete data and negative margins, DCISionRT divided 52% women into Elevated (DS > 3) and 48% in Low (DS ≤ 3) Risk groups. In the Elevated Risk group, RT significantly decreased relative 10-year ipsilateral total recurrence (TotBE) and 10-year ipsilateral invasive recurrence (InvBE) rates, HR 0.32 and HR 0.24, with absolute decreases of 15.5% and 9.3%. In the Low Risk group, there were no significant risk differences observed with radiotherapy. Using a cutoff of DS > 3.0, the test was not predictive for RT benefit (p = 0.093); however, above DS > 2.8 RT benefit was greater for InvBE (interaction p = 0.038). Recurrences at 10 years without radiotherapy increased significantly per 5 DS units (TotBE HR:1.5 and InvBE HR:1.5). Continuous DS was prognostic for TotBE risk although categorical DS did not reach significance. Absolute 10-year TotBE and InvBE risks appear sufficiently different to indicate that DCISionRT can aid physicians in selecting individualized adjuvant DCIS treatment strategies. Further analyses are planned in combined cohorts to increase statistical power.