Background: Adjuvant detection of minimal residual disease (MRD) via plasma circulating tumor DNA (ctDNA) analysis is strongly associated with recurrence of early-stage breast cancer (BC). While this test is now available to oncologists and to patients, it is unclear how the testing is being used in clinical practice and whether results influence clinical decision-making.

Objective: We delved into our institutional experience with adjuvant ctDNA testing in BC to examine testing patterns and management changes based on +ctDNA results.

Methods: This study included 383 patients with early-stage BC who had plasma ctDNA testing via a clinically validated, personalized, tumor-informed mPCR-NGS ctDNA assay (Signatera, Natera, Inc.). All tests were ordered at UCLA in the real-world clinical setting between 2019 and 2024. A retrospective chart review was conducted to collect information regarding patients’ BC management. Extracted items included patients’ demographics, tumor characteristics, ctDNA status, and management change due to positive ctDNA results (change in imaging frequency, ctDNA cadence and medication), and dates of important clinical events.

Results: 383 patients with stage I-III BC (ER+/HER2-: 242, HER2+: 66, triple-negative BC [TNBC]: 73 were included. 44 (11.5%) patients had ctDNA+ results at any adjuvant time point and 339 (88.5%) had all ctDNA- results. The detection of adjuvant ctDNA was significantly associated with distant recurrence (DR) (Median DRFS in ctDNA+ of 61.1mon vs. 172.1mon in ctDNA- group from surgery), with a median lead time of 13.3 months from first +ctDNA to DR.

Among the 44 ctDNA+ patients, 36/44 (81.8%) had changes in management. 32/44 (72.7%) underwent re-staging scans due to +ctDNA, and 11/32 (34.3%) were found to have distant metastasis, including 7/11 patients had metastasis identified prior to development of clinical symptoms. In contrast, 21/32 (65.6%) patients did not have radiographic evidence of DR on immediate imaging, although 10/21 patients were later found to have local or distant recurrences.

Additionally, 12/44 (28.3%) patients with ctDNA+ had a documented change in ctDNA monitoring cadence, including 11 patients transitioned from a testing cadence of every 3-6 months to every 1-3 months. 7/44 (15.9%) patients had adjustment to their cancer medication regimens due to ctDNA+ results, with 4/7 (57.1%) patients achieving ctDNA clearance, and 3/7 (42.9%) patients exhibiting persistently increasing ctDNA levels.

Conclusions: The detection of ctDNA impacted clinical care in most patients. Most patients had a re-staging scan triggered by the positive ctDNA result. A subset of patients had a change in systemic therapy with subsequent ctDNA clearance. These data guide future prospective MRD studies aimed at therapeutic interception to improve BC outcomes.