ctDNA MRD Test Identifies Breast Cancer Patients Who May Avoid Surgery

Selecting surgery versus non-surgical management in early-stage breast cancer can be challenging for older patients, who often balance disease control with comorbidities and quality-of-life considerations. Primary endocrine therapy is a recognized alternative to surgery in this group, but practical tools to stratify risk and monitor response have been limited. A newly published study now reports that a circulating tumor DNA-based molecular residual disease test can help identify which patients may safely pursue endocrine therapy without surgery.

Natera’s Signatera molecular residual disease (MRD) assay was evaluated in a prospective study of older women with early-stage ER+/HER2- breast cancer published in Clinical Cancer Research. The study enrolled 43 women aged 70 years and older who elected to forgo surgery and receive primary endocrine therapy (pET). Participants underwent baseline Signatera testing and serial assessments every three to six months in parallel with standard imaging and clinician evaluation.

Baseline MRD testing categorized patients by circulating tumor DNA (ctDNA) status, with 68% (23 of 34 with available baseline results) testing negative and experiencing no progression, yielding a 100% negative predictive value at baseline. Among 11 patients who were MRD-positive at baseline, 64% (7 of 11) cleared ctDNA after six months of pET; all seven remained free of distant progression, and one experienced locoregional progression detected by Signatera before imaging. Across the cohort, five progression events occurred, each preceded by MRD positivity, corresponding to 100% longitudinal sensitivity for progression detection.

More than 80% of participants reported that Signatera informed their treatment decisions without increasing anxiety. Serial molecular monitoring aligned with imaging findings and supported physician assessment during non-surgical management. The results underscore the potential utility of MRD-guided monitoring in older patients deferring surgery within this clinical context.

“Treatment decisions for older patients with breast cancer often require balancing disease control with quality of life, other medical problems and patient preference,” said Priscilla F. McAuliffe, M.D., Ph.D., lead author of the study and a surgical oncologist at the University of Pittsburgh. “The findings from this study suggest ctDNA monitoring with Signatera could help identify patients for whom non-surgical approaches for their breast cancer treatment may be appropriate.”

“This study highlights the role of Signatera as a critical molecular monitoring tool for patients with breast cancer who defer surgery,” said Angel Rodriguez, M.D., senior medical director of oncology at Natera. “By providing an early signal of disease progression that aligns with imaging, Signatera may help physicians monitor treatment response and make more informed care decisions for older patients.”

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