Signatera's Molecular Residual Disease Testing Shows Powerful Risk Stratification in Early-Stage Breast Cancer

Researchers at Natera Inc. (NTRA) have released pivotal translational findings from the PALLAS Phase III investigation, demonstrating that molecular residual disease (MRD) assessment following surgery significantly outperforms traditional clinical variables in predicting recurrence outcomes for HR+/HER2- breast cancer patients. The data, unveiled at the San Antonio Breast Cancer Symposium, draws from 420 U.S. patients who underwent MRD testing using the Signatera Genome platform at multiple post-operative intervals.

Striking Risk Separation Through MRD Stratification

The most compelling finding centers on MRD status’s ability to distinguish patient populations with vastly different recurrence trajectories. Among the 92% of patients who tested MRD-negative at baseline, the five-year distant recurrence-free interval (DRFI) reached 93%, maintaining at 95% by end-of-treatment. In stark contrast, the 8% of patients with baseline MRD positivity faced just a 28% five-year DRFI—representing a hazard ratio of approximately 15. This gap widened even further by treatment completion, with MRD-positive patients showing 32% DRFI and hazard ratios exceeding 20 compared to their MRD-negative counterparts.

Consistent Predictive Performance Across Treatment Timeline

MRD status assessments via circulating tumor DNA (ctDNA) were conducted at three critical timepoints: treatment initiation, six-month evaluation, and end-of-treatment after two years of palbociclib combined with endocrine therapy. Across all measurement windows, molecular residual disease consistently demonstrated hazard ratios between 13.4 and 21.5 for MRD-positive versus MRD-negative patients—substantially exceeding the risk discrimination provided by conventional clinicopathologic factors alone.

Clinical Implementation Pathway

These findings support incorporating MRD testing into routine post-surgical assessment protocols, enabling clinicians to tailor treatment intensity based on individual molecular risk profiles. This molecular-guided approach promises more precise patient stratification than histopathological features, potentially allowing de-escalation strategies for low-risk MRD-negative patients while intensifying surveillance for the high-risk MRD-positive cohort. Additional datasets from non-U.S. populations and pre-specified subgroup analyses remain pending.