Is circulating tumor DNA the best surveillance tool for detecting post-adjuvant relapse in stage I-III breast cancer patients?

Abstract

e12505 Background: Despite advances made in breast cancer management, sensitive methods to detect relapse are limited to clinical examination and imaging. In this retrospective study, we evaluated the role of circulating tumor DNA (ctDNA) in detecting relapses in breast cancer patients on routine surveillance after completing definitive treatments. Methods: We analyzed data from a cohort of 298 stage I-III breast cancer patients (all subtypes) undergoing routine surveillance (on observation only or patients on adjuvant therapies) at our institution. These patients were followed with serial quarterly or semiannual ctDNA analysis using Signatera assays, which utilize multiplex PCR-based next-generation sequencing to identify 16 unique single nucleotide variants in a patient's tumor through whole-exome sequencing. True positives were defined as two or more serially positive ctDNA (+ctDNA) results with radiologic confirmation of relapses within 12 months. Demographic, clinical, radiological, and laboratory data were collected for patients with disease progression observed during surveillance. Results: Among the 298 patients included in our analysis, 289 patients had negative ctDNA results. These patients did not experience relapses on standard surveillance, thus resulting in a negative predictive value of 100%. Nine patients had a +ctDNA test (Table 1), among which seven were true positives. The median time from the +ctDNA test to radiologic relapse was 7 weeks. The two false positive cases had no radiological relapse and repeat ctDNA testing was negative. Therefore, in our analysis, sensitivity was 100%, specificity was 99.3%, with a positive predictive value of 99.9%. Notably, only one true-positive patient exhibited clinical symptoms during ctDNA positivity, while the remainder were clinically asymptomatic. Conclusions: Our study reveals that serial ctDNA analysis is a highly sensitive and specific method for detecting disease relapses in stage I-III breast cancer patients during routine surveillance compared to standard surveillance. Future prospective studies are warranted to better understand the role of ctDNA in advocating personalized surveillance. ctDNA positive patients with disease progression. Patient Age (years) Staging Time to radiologic relapse (weeks) 1 76 III 33 2 46 II 1 3 81 III 30 4 36 III 11 5 # 49 II 7 6 75 I 3 7 62 II 5 8* 54 II NA 9 * 53 II NA *: False positives; #: Clinically symptomatic; NA: Not applicable.