PALLAS Trial Reveals How MRD Testing Could Transform Breast Cancer Risk Prediction

Natera Inc. (NTRA) has unveiled significant clinical findings that could reshape how doctors assess recurrence risk in early-stage breast cancer. The company presented new translational research from its Phase III PALLAS trial at the San Antonio Breast Cancer Symposium, demonstrating that molecular residual disease (MRD) status—detected through the Signatera genome test—serves as a powerful predictor of treatment outcomes in HR+/HER2- breast cancer patients.

The Clinical Breakthrough: Stark Risk Stratification

The most compelling finding emerged from a 420-patient U.S. biomarker cohort: MRD status after surgery and adjuvant therapy creates a dramatic divide in patient prognosis. Among patients who tested MRD-negative at baseline (approximately 92% of the cohort), the five-year distant recurrence-free interval (DRFI) reached 93%. This exceptional outcome remained consistent through treatment, with MRD-negative patients at end-of-treatment (EOT) achieving a 95% five-year DRFI.

The contrast with MRD-positive patients tells a different story entirely. This smaller subset—roughly 8% of the population—faced substantially higher recurrence risk. Baseline MRD-positive patients showed a five-year DRFI of only 28%, while those remaining MRD-positive at EOT achieved 32%, representing hazard ratios of approximately 15 and exceeding 20 respectively compared to MRD-negative counterparts.

Why PALLAS Data Matters for Clinical Practice

In the PALLAS trial, stage II-III HR+/HER2- breast cancer patients received two years of palbociclib (a CDK4/6 inhibitor) combined with endocrine therapy. Researchers conducted Signatera MRD assessments at three critical timepoints: baseline, six months into treatment (C6D1), and at the end of the two-year protocol.

Across all measurement windows, ctDNA status proved consistently and robustly associated with recurrence risk—a finding that held true even after adjusting for traditional clinical and pathological factors. The risk separation achieved through MRD testing (hazard ratios ranging from 13.4 to 21.5 for positive versus negative patients) far exceeded what clinicians typically observe with conventional prognostic markers alone.

Toward Personalized Breast Cancer Management

These PALLAS results support integrating MRD testing into routine post-surgical assessment protocols. By identifying which patients face genuinely low recurrence risk and which require enhanced surveillance or intervention strategies, Signatera MRD testing enables a more nuanced, personalized approach to early-stage HR+ breast cancer management.

Additional datasets from international cohorts and detailed subgroup analyses are forthcoming, promising to further clarify MRD’s role in diverse patient populations.