SAGA Diagnostics, a pioneer in tumor-informed blood-based cancer detection and precision medicine redefining the standard for ultrasensitive and early molecular residual disease (MRD) detection, today announced the publication of a new study in EMBO Molecular Medicine, titled “NeoCircle: pre- and post-operative circulating tumor DNA dynamics predicts survival in neoadjuvant-treated early breast cancer.”
NeoCircle is a prospective real-world clinical study for ctDNA monitoring of patients with early breast cancer (eBC) eligible for neoadjuvant therapy (NAT), as a sub-cohort within the SCAN-B study (NCT02306096). NeoCircle was designed to evaluate the clinical utility of structural-variant (SV)-based circulating tumor DNA (ctDNA) detection and to ascertain its usefulness for assessing response to NAT. ctDNA analysis was performed for 136 NAT-eligible patients comprised of all breast cancer subtypes. The findings validate SVs as a clinically relevant MRD biomarker in eBC, demonstrating that ctDNA monitoring across both neoadjuvant and adjuvant treatment can predict disease progression months to years in advance and inform clinical outcomes, including survival.
“With unmatched sensitivity, detecting structural variants at levels as low as 1 part in 10 million, Pathlight provides the resolution needed to identify true molecular residual disease at its earliest stages,” said Lao Saal, MD, PhD, Head, Division of Translational Oncogenomics, and Co-Director, CIRCE Women’s Cancer Research Center, Lund University. “The NeoCircle study, with up to 9.7 years of clinical follow-up, offers a comprehensive view of the durability of SVs and the potential for clinical impact incorporating this approach in the care plan for patients with cancer.”
While pathological complete response (pCR) remains an established prognostic marker, its limited ability to stratify the heterogeneous non-pCR majority highlights a critical need for more precise tools. ctDNA enables real-time tracking across treatment settings, in which persistent or re-emerging signals indicate evidence for MRD and high-risk of recurrence, as described here in the NeoCircle study using Pathlight.
Key Highlights:
- The analysis cohort included 85.3% of Stage I and II breast cancer patients, where the opportunity for curative intent remains high.
- Complete or partial clearance of ctDNA during NAT was a significant predictor of favorable outcome, with only 10.4% of patients experiencing recurrence compared to 56.3% for the ctDNA non-response group.
- Lack of ctDNA clearance after completion of NAT was a significant predictor of poor breast cancer-free interval (BCFi) and overall survival (OS), outperforming pCR.
- ctDNA positivity at the post-surgical landmark timepoint was a significant predictor of worse BCFi and OS, with 91% of patients who did not clear ctDNA showing non-pCR.
- Detection of ctDNA during post-operative adjuvant monitoring preceded clinical relapse by up to 4 years (median of 13.8 months), highlighting the potential for earlier intervention.
- ctDNA detection achieved 86.7% overall sensitivity for distant recurrence, increasing to 92.9% for pathologically confirmed cases and 81.0% when including local and CNS-only relapses.
“SVs represent a foundational biomarker for detecting molecular recurrence before it becomes clinically apparent,” said Wendy Levin, MD MS, Chief Clinical Officer of SAGA Diagnostics. “The early origin of SVs in tumorigenesis, stability under treatment pressure, and resistance to confounding signals enable ultra-sensitive, tumor-informed detection. With 85% of patients in this analysis having Stage I-II disease, where curative intent remains high, we see a clear path toward integrating these biomarkers into clinical practice. This can help guide treatment decisions in real-time, with the potential to improve patient outcomes, including long-term survival.”
Click here to read the full publication.
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.
For more information, visit www.sagadiagnostics.com
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