SAGA Diagnostics Highlights Clinical Validity of Pathlight™ MRD in TNBC During SABCS Presentations
SAGA Diagnostics Highlights Clinical Validity of Pathlight™ MRD in TNBC During SABCS Presentations. SAGA Diagnostics®, a leader in blood-based cancer detection and precision oncology, continued to advance clinical understanding of molecular residual disease (MRD) this week with multiple presentations at the San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas. The company and its collaborating investigators reported new data from two clinical studies focused on triple-negative breast cancer (TNBC), building on a growing body of evidence demonstrating Pathlight™ MRD’s ability to detect circulating tumor DNA (ctDNA) with exceptional sensitivity in early-stage disease.
SAGA Diagnostics has positioned itself at the forefront of ultra-sensitive MRD detection by applying advanced sequencing approaches centered on structural-variant analysis. This design allows detection of ctDNA at extremely low allele frequencies, supporting earlier MRD identification, longitudinal monitoring, and potential tailoring of treatment in real time. As the oncology community continues to evaluate how MRD guides clinical decisions, these new presentations contribute important data regarding how ctDNA dynamics relate to tumor response, recurrence risk, and event-free survival in TNBC.
Building on TRACER: A Growing Evidence Base
Both the Neo-N Phase 2 trial and the Dana-Farber Cancer Institute Multi-Center Registry build directly on the results of SAGA’s sentinel TRACER study, which previously demonstrated strong analytical and clinical performance of Pathlight in early-stage breast cancer. An expanded TRACER analysis, also highlighted during SABCS, reinforced the diagnostic strength of the platform’s structural-variant–anchored detection strategy. Investigators emphasized that the Pathlight design consistently uncovered ctDNA across a range of tumor subtypes and time points, showing outstanding sensitivity, precision, and reliability.
As more institutions evaluate MRD as a biomarker capable of improving clinical management, these results further support Pathlight’s role across research settings and potential future integration into routine breast cancer care.
Neo-N Phase 2 Trial: ctDNA Dynamics Linked to Pathologic Response and Event-Free Survival
One of the key studies presented at SABCS was the Neo-N Phase 2 trial, conducted in collaboration with Dr. Sherene Loi at the Peter MacCallum Cancer Center and the Breast Cancer Trials Cooperative Group in Australia. Neo-N evaluated whether changes in ctDNA during neoadjuvant therapy could be used to predict treatment response and guide escalation or de-escalation strategies in early-stage TNBC.
Patients in the study received neoadjuvant carboplatin and paclitaxel combined with nivolumab. The trial assessed whether ctDNA clearance during therapy correlated with pathologic complete response (pCR)—a critical indicator of long-term prognosis—and with event-free survival (EFS), a major clinical endpoint.
Baseline ctDNA was detected in 91% of early-stage (stage I–II) patients, demonstrating the high detectability required for nearly universal MRD monitoring. Investigators observed that early elimination of ctDNA during treatment strongly associated with improved outcomes. For on-treatment ctDNA-positive patients, no pathologic complete responses were recorded and the three-year event-free survival rate was 45%. By contrast, patients who became ctDNA-negative during therapy achieved a three-year EFS of 90%, demonstrating a pronounced difference between groups.
Dr. Sherene Loi noted that these findings indicate the potential of ctDNA trajectories to inform real-time decision-making. According to Dr. Loi, early ctDNA clearance reflects treatment responsiveness and could one day support personalized therapeutic plans by identifying which TNBC patients may safely de-escalate treatment intensity and which may require an intensified approach. Such information, she explained, may complement traditional surgical endpoints and contribute to precision oncology strategies.
Dana-Farber TNBC Multi-Center Registry: MRD and Predictive Insights During Preoperative Therapy
A second major data set presented at SABCS came from a collaborative registry study with Dr. Heather Parsons and colleagues at the Dana-Farber Cancer Institute, examining the relationship between MRD detection, therapeutic response, and pathologic outcomes in early TNBC. This trial also evaluated how MRD persisted or resolved during preoperative systemic therapy and whether clearance linked to pCR.
In the adjuvant setting, Pathlight exhibited 100% sensitivity and 99% specificity. These results represent a highly accurate performance profile, especially in a disease subtype known for aggressive behavior and rapid recurrence risk.
Among 80 registry participants, Pathlight detected ctDNA in 93.4% of patients at diagnosis, again demonstrating broad applicability for on-treatment monitoring. Clearance of ctDNA during therapy correlated with a high negative predictive value for pCR. During systemic treatment, negative predictive value reached 78.4%, increasing to 85.7% among patients receiving immunotherapy. Preoperatively, the negative predictive value was 71.8%.
Of particular clinical relevance, patients with pathologic residual disease frequently had detectable ctDNA after surgery. These patients continued to show ctDNA persistence despite receiving adjuvant therapy, and all ultimately experienced disease recurrence. According to investigators, these findings suggest MRD could help identify patients at persistent high risk who may benefit from alternative or intensified therapeutic intervention.
Dr. Parsons emphasized the significance of evaluating MRD in the context of Keynote-522, which established a new standard of care in TNBC treatment through incorporation of immunotherapy. She noted that ctDNA-based monitoring may become an important tool for personalized risk assessment, response evaluation, and long-term disease management. Future interventional trials, she added, are expected to help determine how clinicians might best integrate ctDNA results into daily practice.
Looking Ahead: Expanding MRD Clinical Utility
Beyond TNBC, Pathlight MRD will continue to be evaluated in new studies, including a planned interventional Phase II trial focused on high-risk ER+/HER2– early breast cancer. In this setting, Pathlight will support long-term surveillance and potentially guide post-neoadjuvant treatment strategies. The CLAIRE Trial aims to refine how MRD detection informs patient selection for additional intervention. Those identified at elevated risk based on persistent ctDNA will be eligible for enrollment into the CATER-MRD Trial, which will measure ctDNA clearance following treatment with metronomic capecitabine.
These initiatives underscore a broader shift across oncology research: using ctDNA not solely as a prognostic marker but as a decision-making tool to tailor therapies in real time. By identifying residual disease earlier than conventional imaging or pathology, MRD could help prevent recurrence or ensure timely therapeutic escalation, ultimately improving patient outcomes and quality of life.
Wendy Levin, MD, MS, Chief Clinical Officer of SAGA Diagnostics, stated that anchoring Pathlight MRD detection to truncal structural variants provides a stable genomic signal and an unparalleled sensitivity profile. According to Dr. Levin, this enables clinicians to gain greater confidence in early therapeutic decisions and may lay the groundwork for MRD-guided management becoming a routine component of breast cancer care.
A Step Toward Personalized Neoadjuvant and Adjuvant Care
Taken together, the Neo-N and Dana-Farber studies expand the clinical evidence showing how ultra-sensitive ctDNA monitoring offers actionable insight into tumor response and recurrence risk in early-stage TNBC. The strong association between MRD clearance and improved outcomes provides compelling motivation for continued evaluation of MRD-guided strategies in clinical trials. While further prospective interventional results will be needed before MRD becomes a routine clinical standard, these data presented at SABCS represent an important step forward in precision-guided treatment for aggressive breast cancer subtypes.
About SAGA Diagnostics
SAGA Diagnostics® is redefining the early detection of molecular residual disease (MRD), empowering treatment decisions with greater insight and confidence. Pathlight™, 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.
