Abstract A012: Using clinical characteristics and molecular markers to predict the risk of subsequent ipsilateral breast events after excision of DCIS

Purpose: To examine incremental values of estrogen receptor (ER) status, body mass index (BMI), menopausal status, and a multi-gene classifier over commonly used clinical factors (i.e. age, tumor grade, comedonecrosis, surgical margins, and treatment) in predicting risk of ipsilateral recurrence (IR) within five years after DCIS diagnosis. Methods: A derivation cohort consisted of participants in the discovery cohort, a retrospective multicenter cohort study in women undergoing surgical resection for DCIS between 01/01/1998 and 02/29/2016. The validation cohort provided cases meeting the same eligibility criteria as the discovery cohort. This analysis includes 313 participants with RNA-seq data who either developed IR 1-5 years after initial DCIS diagnosis or were free from subsequent breast events at least five years. Cox proportional hazards regression was used to estimate hazard ratios (HRs) of IR in 216 TBCRC participants (76 with IR). We developed the clinical score using clinical predictors (aforementioned clinical factors and ER) and their regression coefficients from the model with the maximum predictive accuracy (e.g. c-index) and the minimum number of predictors, and the summary score integrating the clinical score and multi-gene classifier. Predictive performance of clinical and summary scores was validated in 97 RAHBT patients (20 with IR). Results: In the discovery cohort, ER negativity, but not BMI or menopausal status, was independently associated with a higher IR risk (HR=2.06, 95% CI 1.18-3.58), and adding ER to the clinical factors-based model increased predictive accuracy (c-index 0.68 to 0.70). The clinical score-adjusted HR was 14.96 (95% CI 8.64-25.91) for multi-gene classifier. Summary scores were better in predicting IR risk than clinical scores (c-index 0.82 vs. 0.70). Compared with their low-risk counterparts, the HR was 4.79 (95% CI 2.55-8.98) in the clinical score-defined high-risk group and 29.02 (95% CI 14.23-59.15) in the summary score-defined high-risk group. In the validation cohort, model performance was improved using summary scores as compared to clinical scores (c-index 0.74 vs. 0.58). Conclusion: Combination of clinical factors and multigene classifier provided more accurate risk estimates of IR within five years after excision of DCIS than clinical factors alone. Citation Format: Graham A. Colditz, Ying Liu, Siri H. Strand, Lorraine King, Jeff Marks, Carlo Maley, Robert B. West, E. Shelley Hwang. Using clinical characteristics and molecular markers to predict the risk of subsequent ipsilateral breast events after excision of DCIS [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr A012.