Signatera MRD identifies breast cancer patients who can forgo surgery
Prospective study published in Clinical Cancer Research shows that women >70 who tested Signatera MRD-negative could avoid surgery and remain progression-free
28 Apr 2026
Natera, Inc., a global leader in cell-free DNA and precision medicine, has announced Clinical Cancer Research has published a study1 showing that Signatera was able to identify older women with early-stage ER+/HER2- breast cancer who can be managed with primary endocrine therapy (pET), without surgery.
While pET can be an alternative to surgery for patients with early breast cancer, tools for risk stratification and monitoring have been limited. This prospective study enrolled 43 women, aged 70 and older, with stage 1-3 ER+/HER2- breast cancer who all elected to forgo surgery and receive pET.
Patients were tested with Signatera at baseline (pre-treatment), and then every 3-6 months alongside standard imaging and physician assessment.
Key results included:
- Pre-treatment (baseline) molecular residual disease (MRD) assessment identified that 68% of patients (23/34) were MRD-negative, among whom zero experienced progression (100% negative predictive value at baseline).
- Among the 11 patients who tested baseline MRD-positive, 64% (7/11) cleared their circulating-tumor DNA (ctDNA) after 6 months of pET, where all 7 remained free of distant progression, and 1 out of 7 experienced locoregional progression that was detected by Signatera in advance of imaging.
- Tumor progression occurred in 5 patients, all of whom tested MRD-positive in advance of imaging (longitudinal sensitivity of 100%).
- Over 80% of patients reported that Signatera helped inform their treatment decisions without increased anxiety.
“Treatment decisions for older patients with breast cancer often require balancing disease control with quality of life, other medical problems and patient preference,” said Dr. Priscilla F. McAuliffe, 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.”
Dr. Angel Rodriguez, senior medical director of oncology at Natera, added, “This study highlights the role of Signatera as a critical molecular monitoring tool for patients with breast cancer who defer surgery. 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.”
References
1. Carleton N, Chang AC, Chen F, Puhalla SL, et al. Use of ctDNA in Older Women with ER+ Breast Cancer to Facilitate Surgical De-escalation: A Prospective, Hybrid-Decentralized Trial with Correlative Studies. Clin Cancer Res OF1–OF11. March 19 2026. https://doi.org/10.1158/1078-0432.CCR-25-4079.