Abstract F1-3: Defining recurrence risk for DCIS: How do we tailor therapy
Authors: Van Zee Kimberly 
Published: March 2023

Abstract
In tailoring treatment for DCIS, the goal is to avoid overtreatment while minimizing risk of recurrence. This necessitates estimation of recurrence risk and assessment of efficacy of each intervention in reducing risk. There are several clinicopathologic and treatment factors that have been proven in prospective trials to affect risk. These have been combined into a multivariable nomogram that estimates 10-year risk of recurrence (DCIS Nomogram). It is available online and free-of-charge, and has been validated in at least 5 independent populations with assessments of calibration and discrimination to assess its utility.
There have also been attempts to develop genomic predictors of risk. The Oncotype DCIS score originally was based on a purely genomic analysis, but was “refined” to include clinicopathologic factors. DCISionRT was initially created with the inclusion of clinicopathologic factors. Neither has been prospectively validated and neither has published any assessments of calibration and discrimination. It is unclear what proportion of either risk estimate is due to the inclusion of clinicopathologic factors vs the actual genomic analysis. Both cost thousands of dollars.
Furthermore, neither the refined Oncotype DCIS score nor the DCISionRT score incorporates the use of endocrine therapy. Tamoxifen and aromatase inhibitors have been proven to reduce the risk of recurrence by about 30-50%, and their use should be expected to decrease risk of recurrence. Yet, neither score accounts for this fact, and therefore the risk predictions are too high for those that take endocrine therapy, and too low for those that do not.
In a sample of 59 women age ≥50 years old, with DCIS ≤2.5cm in size and clear margins, 10-year recurrence risk estimates from the DCIS Nomogram and refined Oncotype DCIS score (RDS) were compared. Overall, RDS risk estimates were in agreement (within 1-2% of the nomogram risk estimate range, calculated with and without the use of endocrine therapy) in 92% of cases. Among the 5 patients for which the Nomogram and RDS estimates disagreed, all had close margins (≤2mm). Close margins are associated with a statistically significant doubling of risk of recurrence. Nevertheless, the Oncotype DCIS score 10-year recurrence estimate was only 5-8% for these patients with close margins, while the Nomogram estimates were 11-14% (assuming use of endocrine therapy) or 21-27% (without endocrine therapy). From all published data, it seems clear that the refined Oncotype DCIS score markedly underestimates risk for those with close margins. And for those with clear margins, there was excellent (100%) agreement between the Nomogram and the refined Oncotype DCIS score.
Given the need for cost-based value in health care, and given the cost-free availability of a validated predictive online DCIS nomogram, rigorous evaluation of predictive accuracy and proof of significant added clinical benefit should be performed and made available before any new expensive commercially available test is adopted for clinical use.
Citation Format: Kimberly Van Zee. Defining recurrence risk for DCIS: How do we tailor therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr F1-3.