Real-world (rw) ctDNA testing trends and associated outcomes in patients (pts) with early stage breast cancer (EBC).

555 Background: Emerging evidence from prospective studies underscores the prognostic potential of ctDNA to inform risk stratification and clinical decision-making in EBC (stage I-III). However, its use and correlation with outcomes in routine clinical practice remains less understood. We describe tumor-informed ctDNA testing trends and the association of test results with recurrence risk among pts with EBC in the rw setting. Methods: Pts with an EBC diagnosis (dx) after 1/1/2018 who had documented HR/HER2 status at initial dx, surgery, and ≥1 commercial ctDNA test in the early stage setting were selected using machine learning models from the Flatiron Health US-nationwide EHR-derived, deidentified, longitudinal database of >750 000 pts with BC (data cutoff 8/31/2024). ctDNA positivity (ctDNA+) was defined as having ≥1 positive test in EBC. Baseline characteristics were stratified by EBC subtype and ctDNA status. To examine the association of ctDNA status with recurrence, unadjusted Kaplan-Meier (KM) plots and adjusted Cox proportional hazards models were performed to assess recurrence-free survival among ctDNA-tested pts, controlling for age, race/ethnicity, stage, ECOG status, dx year, insurance status, practice type, and neoadjuvant/adjuvant treatment. Recurrence was indexed to surgery date and defined as locoregional or metastatic recurrence or death. Results: In a cohort of 195 279 pts with EBC, 14 496 ctDNA tests were performed in 4639 pts (median 2 per pt) with most in stage I (43.3%) and II (37.1%). Testing prevalence was highest in HR-/HER2- (4.9%), followed by HR-/HER2+ (3.5%), HR+/HER2+ (2.9%), and HR+/HER2- (1.9%). Testing increased from 1.6% (n = 450) of EBC pts dx in 2020 to 4.25% (n = 1278) in 2023 with a decrease in median time to first test pre- and post-2022 (35 vs 8 months respectively). Among tested pts, 921 (19.9%) had ≥1 positive test and were more likely to be younger (58 vs 64 years) and have stage III disease compared to non-tested pts. ctDNA+ patients had a worse 3-year overall survival (OS) as well as a strong association with recurrence (Table). Conclusions: In the largest rw study of ctDNA testing in EBC to date, pts with ctDNA+ disease across all subtypes were more likely to recur, highlighting the potential prognostic value of ctDNA testing to inform pt counseling, monitoring and treatment strategies. These rw results, coupled with findings from prospective randomized trials, support the case for ctDNA+ as a distinct risk category in the management of EBC. Unadjusted 3-year OS probability (95% CI) EBC Subtype ctDNA- pts ctDNA+ pts Adjusted HR (95% CI) All with P <0.01 HR+/HER2-N = 2786 0.98 (0.97-0.99) 0.76 (0.7-0.82) 10.7 (7.08-16.1) HR-/HER2-N = 1002 0.96 (0.95-0.98) 0.61 (0.52-0.72) 10.7 (6.34-18.1) HR+/HER2+N = 592 0.97 (0.95-0.99) 0.85 (0.77-0.94) 11.8 (4.54-30.8) HR-/HER2+N = 259 0.97 (0.94-1) 0.78 (0.62-0.97) 8.94 (1.72-46.4)