SAGA Diagnostics Highlights NeoCircle Publication Showcasing Prognostic Impact of ctDNA Dynamics in Early Breast Cancer
SAGA Diagnostics has announced the publication of new clinical research highlighting the potential of ultrasensitive circulating tumor DNA (ctDNA) monitoring to transform the management of early breast cancer. The study, published in EMBO Molecular Medicine and titled “NeoCircle: pre- and post-operative circulating tumor DNA dynamics predicts survival in neoadjuvant-treated early breast cancer,” provides evidence that structural variant (SV)-based ctDNA analysis can identify molecular residual disease (MRD) and predict recurrence long before traditional clinical signs emerge.
The findings stem from the NeoCircle study, a prospective real-world clinical investigation focused on patients with early breast cancer who were eligible for neoadjuvant therapy (NAT). The study was conducted as a sub-cohort within the larger SCAN-B Study clinical research program. Researchers designed NeoCircle to evaluate whether structural variant-based ctDNA detection could serve as a reliable biomarker for monitoring treatment response and forecasting long-term outcomes in breast cancer patients undergoing therapy before surgery.
The study evaluated ctDNA data from 136 patients representing all major breast cancer subtypes. Importantly, more than 85% of the cohort consisted of patients with Stage I or Stage II disease, where treatment is often pursued with curative intent. Researchers tracked ctDNA levels before, during, and after therapy to determine whether molecular changes in blood samples could provide earlier and more accurate insights into disease status compared with traditional assessment methods.
The publication adds to growing evidence supporting ctDNA as a powerful tool in precision oncology. Molecular residual disease refers to microscopic cancer cells that remain in the body after treatment but cannot yet be detected through imaging or routine clinical examinations. These residual cells may eventually lead to relapse, making earlier detection critical for improving patient outcomes. By monitoring ctDNA, clinicians may be able to identify high-risk patients months or even years before conventional recurrence becomes clinically apparent.
At the center of the study is SAGA Diagnostics’ Pathlight platform, which is designed for ultra-sensitive tumor-informed detection of structural variants. Structural variants are large-scale genomic alterations that occur early in tumor development and tend to remain stable over time, even under treatment pressure. Because of these characteristics, they are increasingly viewed as promising biomarkers for MRD detection.
According to the company, the Pathlight platform can detect structural variants at extremely low levels, down to one part in ten million. This degree of sensitivity may allow clinicians to identify residual disease earlier than many currently available ctDNA technologies.
Dr. Lao Saal, Head of the Division of Translational Oncogenomics and Co-Director of the CIRCE Women’s Cancer Research Center at Lund University, emphasized the significance of the findings and the technological capabilities behind the research. He noted that the NeoCircle study provides one of the most comprehensive evaluations to date of structural variants as biomarkers in breast cancer, supported by clinical follow-up extending nearly a decade.
The study followed patients for up to 9.7 years, allowing researchers to examine how ctDNA dynamics correlated with long-term survival outcomes. The data demonstrated that ctDNA monitoring during both neoadjuvant and adjuvant treatment phases could predict disease progression significantly earlier than conventional clinical detection methods.
One of the most important findings involved ctDNA clearance during neoadjuvant therapy. Researchers observed that patients who experienced complete or partial ctDNA clearance during treatment had substantially better outcomes than patients whose ctDNA signals persisted. Only 10.4% of patients classified as ctDNA responders experienced recurrence, compared with 56.3% of patients who failed to clear ctDNA during therapy.
These results suggest that ctDNA dynamics may provide a highly informative measure of treatment effectiveness in real time. Rather than relying solely on imaging or surgical pathology after treatment completion, clinicians may eventually use ctDNA monitoring to adjust therapy earlier and more precisely.
The study also compared ctDNA monitoring with pathological complete response, or pCR, which is currently considered one of the most important prognostic markers in early breast cancer treated with neoadjuvant therapy. Pathological complete response refers to the absence of detectable cancer cells in tissue samples following treatment.
While pCR remains clinically valuable, the NeoCircle study highlighted important limitations of the marker, particularly for the large group of patients who do not achieve complete response. Researchers found that lack of ctDNA clearance after neoadjuvant therapy was a stronger predictor of poor breast cancer-free interval and overall survival than pCR alone.
The findings indicate that ctDNA monitoring could help stratify risk among patients who fall into the heterogeneous non-pCR population, potentially enabling more personalized post-treatment management strategies. Patients who remain ctDNA-positive after treatment may benefit from intensified surveillance or additional therapeutic interventions aimed at preventing relapse.
Another key observation involved ctDNA positivity following surgery. Researchers found that patients with detectable ctDNA after surgical treatment experienced significantly worse breast cancer-free intervals and overall survival outcomes. Among patients who failed to clear ctDNA at this post-surgical landmark, 91% also showed non-pCR status, further reinforcing the connection between persistent molecular disease and higher recurrence risk.
Perhaps one of the most clinically impactful findings was the ability of ctDNA monitoring to predict relapse far in advance of traditional diagnosis. During post-operative adjuvant monitoring, ctDNA detection preceded clinical recurrence by as much as four years, with a median lead time of approximately 13.8 months.
This early warning capability could eventually reshape cancer surveillance practices. Detecting relapse earlier may provide oncologists with an opportunity to intervene before overt metastatic disease develops, potentially improving long-term outcomes and survival rates.
The study also demonstrated strong sensitivity for recurrence detection overall. ctDNA analysis achieved 86.7% sensitivity for distant recurrence detection. Sensitivity increased to 92.9% among pathologically confirmed recurrence cases and remained robust at 81% when local recurrences and central nervous system-only relapses were included in the analysis.
These findings support the growing belief that ctDNA-based monitoring may become an important component of future oncology care pathways, particularly for patients undergoing treatment with curative intent.
Dr. Wendy Levin, Chief Clinical Officer of SAGA Diagnostics, stated that structural variants represent a foundational biomarker for identifying molecular recurrence before disease becomes clinically visible. She explained that structural variants offer several advantages over other biomarkers because they originate early during tumor formation, remain stable throughout treatment, and are less susceptible to biological noise that can complicate interpretation.
Levin also highlighted the relevance of the study population, noting that most patients had Stage I-II disease, where early intervention and precise treatment adjustments could have a substantial impact on survival. According to her, the findings support a pathway toward integrating structural variant-based ctDNA monitoring into routine clinical practice.
The NeoCircle study reflects broader momentum within oncology toward more personalized and data-driven treatment strategies. As precision medicine continues to evolve, clinicians are increasingly seeking tools capable of providing dynamic, real-time insights into how patients respond to therapy and whether residual disease remains after treatment.
Traditional imaging and pathology assessments provide valuable information but are often limited in their ability to detect microscopic disease burden. ctDNA monitoring offers a minimally invasive approach that may complement existing diagnostic methods and enable more adaptive cancer care strategies.
The publication also underscores the growing importance of tumor-informed approaches to MRD detection. Unlike fixed-panel assays that search for common mutations, tumor-informed technologies are customized using each patient’s unique tumor profile. This personalization may improve specificity and sensitivity, particularly in cancers with complex genomic structures.
For breast cancer specifically, the findings may have important implications as clinicians seek better ways to identify which patients require escalated therapy and which may safely avoid overtreatment. Earlier identification of high-risk patients could improve clinical decision-making while potentially reducing unnecessary toxicity for lower-risk individuals.
As the field of ctDNA research continues to expand, studies such as NeoCircle are helping establish the clinical evidence necessary for broader adoption of molecular monitoring technologies. The long-term follow-up data and strong prognostic associations reported in the study contribute to a growing body of evidence supporting the role of ultrasensitive MRD detection in improving cancer management and patient survival outcomes.
About Pathlight
Pathlight™ MRD is SAGA Diagnostics’ personalized, tumor-informed multi-cancer molecular residual disease (MRD) platform designed for ultra-sensitive detection of circulating tumor DNA (ctDNA). Using a proprietary combination of whole genome sequencing and digital PCR, Pathlight tracks structural variants (SVs) stable genomic biomarkers that enable earlier and more precise detection of cancer recurrence and treatment response monitoring.
With industry-leading sensitivity and specificity, Pathlight helps oncologists make more informed treatment decisions across the patient journey. In its first few quarters on the market, Pathlight has already been adopted by more than 80 cancer centers across the United States, reflecting strong clinical demand for next-generation MRD testing.
Pathlight is Medicare-covered for early-stage breast cancer across all subtypes and is being used in clinical studies by leading academic institutions, national cancer centers, and pharmaceutical companies.
About SAGA Diagnostics
SAGA Diagnostics® is redefining the early detection of molecular residual disease (MRD), empowering treatment decisions with greater insight and confidence. Pathlight™ MRD, the company’s flagship product, is an ultra-sensitive, blood-based, multi-cancer MRD test that is now available for commercial use in the U.S. for patients with early-stage breast cancer.
SAGA is partnering with pharmaceutical and biotechnology companies, as well as commercial entities, to support early through late-stage cancer development programs across a range of cancer types. SAGA’s headquarters and CLIA-certified laboratory are located in the heart of the life science ecosystem in Research Triangle Park, North Carolina. SAGA Diagnostics combines world-class genomic expertise with a leadership team deeply experienced in MRD, all aligned in the mission to intercept cancer at its earliest stages when it is most treatable.
