Monitoring circulating tumor DNA dynamics outperformed standard markers for predicting survival and relapse in early-stage patients.
SAGA Diagnostics announced the publication of the NeoCircle study in the journal EMBO Molecular Medicine, demonstrating the prognostic value of circulating tumor DNA (ctDNA) dynamics in patients with early breast cancer. The study found that the Pathlight molecular residual disease (MRD) platform can detect cancer relapse up to four years before clinical progression.
NeoCircle is a prospective study monitoring ctDNA in 136 patients eligible for neoadjuvant therapy (NAT). The analysis included all breast cancer subtypes, with 85.3% of patients having Stage I or II disease. According to the study, monitoring ctDNA across both neoadjuvant and adjuvant treatment can predict disease progression and survival outcomes.
While pathologic complete response (pCR) is an established prognostic marker, its ability to stratify patients who do not achieve pCR is limited. The study suggests ctDNA enables real-time tracking where persistent signals indicate high risk of recurrence. The lack of ctDNA clearance after completion of NAT was a significant predictor of poor breast cancer-free interval, and overall survival, according to the release.
“The NeoCircle study, with up to 9.7 years of clinical follow-up, offers a comprehensive view of the durability of [structural-variants] and the potential for clinical impact incorporating this approach in the care plan for patients with cancer,” says Lao Saal, MD, PhD, head of the division of translational oncogenomics and co-director of the CIRCE Women’s Cancer Research Center at Lund University, in a release.
Data from the analysis showed that 10.4% of patients who cleared ctDNA during NAT experienced recurrence, compared to 56.3% in the ctDNA non-response group. Detection of ctDNA during post-operative monitoring preceded clinical relapse by a median of 13.8 months. The platform achieved 86.7% overall sensitivity for distant recurrence, which increased to 92.9% for pathologically confirmed cases.
“[Structural-variants] represent a foundational biomarker for detecting molecular recurrence before it becomes clinically apparent,” says Wendy Levin, MD, MS, chief clinical officer of SAGA Diagnostics, in a release. “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.”
The Pathlight MRD platform uses a combination of whole genome sequencing and digital PCR to track structural variants. These genomic biomarkers are stable under treatment pressure and resistant to confounding signals, according to the release. The test is currently covered by Medicare for early-stage breast cancer across all subtypes in the US.
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