Pai, Tanmayi

Background: The current guidelines recommend that women at elevated risk for breast cancer (BC), defined as lifetime BC risk ≥ 20%, undergo annual screening with breast magnetic resonance imaging (MRI) and mammogram. However, limited evidence exists in the literature to guide the optimal timing of the MRI relative to the mammogram. Our study evaluated women undergoing high-risk BC screenings to determine the impact of timing for supplemental MRI on BC detection. Methods: Patients who completed high-risk screening MRI at a single institution from January 2019 through June 2022 were included. Baseline characteristics and clinical outcomes were collected through retrospective chart review. MRI exams were divided into two groups based on timing of MRI: concurrent (<90 days from mammogram) and staggered (≥90 days from mammogram). Results: Of 1115 patients initially identified, 770 met inclusion criteria, with a total of 3707 screening exams performed (2073 mammograms and 1634 MRIs). The final analysis included 1355 MRI exams for 712 patients, where a prior mammogram and MRI were available. Of the MRIs included, 784 (57.9%) were concurrent and 571 (42.1%) were staggered. Additional imaging was performed for 12.5% (98/784) of concurrent MRIs and 9.6% (55/571) of staggered MRIs. Biopsy rates were 9.8% (77/784) for concurrent and 7.0% (40/571) for staggered MRIs. In this high-risk population, there were surprisingly low BC detection rates, with a BC incremental detection rate of 0.5% in both the concurrent and staggered groups (p = 1.0), with the median size of detected invasive BCs equaling 5 mm in the concurrent group and 4 mm in the staggered group (p = 0.72). Conclusions: When comparing concurrent and staggered MRI regimens, there were no significant differences in incremental cancer detection rate, tumor size, rates of additional imaging, or negative biopsies. Further investigation with prospective analysis is needed to validate these findings.

3052 Background: Minimal residual disease (MRD) detected using circulating tumor DNA (ctDNA) is associated with increased breast cancer (BC) relapse risk in patients (pts) with early BC after curative-intent surgery. However, the clinical utility of ctDNA-based MRD testing for post-surgical surveillance and risk stratification remains incompletely defined. We used real-world data to evaluate the performance of Guardant Reveal, a tissue-free epigenomic assay for MRD detection, and the clinical significance of a positive MRD test (+MRD) in pts with resected early BC. Methods: Data of pts with resected stage I-IIIA BC in the Guardant InfinityAI Data Library who underwent Guardant Reveal testing between February 2023 and September 2025 was analyzed. Pts with ≥1 post-surgical MRD were included if they had either no distant metastatic BC recurrence with ≥1 year of follow up after the last MRD test or a documented distant metastatic BC postoperatively; pts with a new non-breast primary malignancy were excluded. Sensitivity was assessed by site of distant metastasis and interval from MRD test to recurrence; nodal recurrences were excluded due to claims data limitations. Specificity was assessed using all tests from pts without recurrence and ≥1 year of follow up after the last post-treatment MRD test. Claims data were used to infer treatment changes following +MRD. Results: A total of 822 pts was analyzed. 114 pts with real-world clinico-genomics data were evaluable for sensitivity and 708 for specificity. One-year sensitivity for distant metastatic recurrence was 71%, and was highest for bone-only (97%, 35/36 cases) or lung (89%, 8/9 cases) recurrences and lowest for brain-only recurrences (33%, 1/4 cases). Sensitivity within 12 months of recurrence was higher in hormone receptor-positive (HR+)/HER2-negative BC (79%) and stage IIIA BC (81%) and for multiple-organ versus single-organ metastasis (83% versus 69%). Sample-level specificity was 94%. Following +MRD, 41 pts did not initiate or switch systemic therapy; 29 had distant BC recurrence, including 24 within 90 days after +MRD. Twenty pts switched therapy within 90 days of +MRD; 19 recurred, including 17 within 90 days after +MRD. Among 10 pts with post-recurrence MRD testing, only 3 had +MRD. Conclusions: In a real-world cohort of pts with resected early-stage BC, a tissue-free epigenomic ctDNA MRD assay demonstrated high specificity and clinically meaningful sensitivity for distant metastatic recurrence, particularly for bone-only and lung metastases and in pts with HR+ BC. These findings support ctDNA-based MRD testing as a noninvasive tool for postsurgical surveillance and risk stratification in early BC.