Related Experiment Video
Updated: Jun 16, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Detection of Circulating Tumor DNA Using a Tissue-Free Epigenomic Assay Is a Highly Prognostic Biomarker in
Foluso O Ademuyiwa1, Cynthia X Ma1, Katherine Weilbaecher1
1Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
Purpose:
Clinical tools to monitor treatment response and metastatic risk could improve early-stage triple-negative breast cancer (TNBC) care. Although molecular residual disease assays show promise, their use in the neoadjuvant setting requires rapid turnaround times. Tissue-informed approaches may be challenging for patients with limited biopsy samples. The objectives were to determine the surveillance sensitivity for detecting metastatic recurrence and evaluate the ctDNA response to neoadjuvant therapy (NAT) using a tissue-free epigenomic assay.
Experimental Design:
Patients with stage II or III TNBC undergoing neoadjuvant docetaxel and carboplatin chemotherapy on a clinical trial (NCT02124902) followed by surgery with or without adjuvant therapy were included in this study. Blood samples were prospectively collected before, during, and after completion of NAT and after surgery at prespecified surveillance time points. Plasma samples were analyzed by Guardant Reveal.
Results:
A total of 119 patients with TNBC were included in the analysis. ctDNA was detected in the postsurgical setting in 8.9% (7/79) of patients, with an 83% (5/6) patient-level surveillance sensitivity for metastatic recurrence and 99.5% (197/198) sample-level specificity. Postsurgical ctDNA detection was prognostic for the shorter recurrence-free interval (HR, 37.7; P < 0.0001). ctDNA detection at the post-NAT presurgical time point was also associated with a shorter recurrence-free interval in patients with residual disease at surgery (HR, 28.2; P < 0.0001).
Conclusions:
In patients with early-stage TNBC, a tissue-free, epigenomic assay demonstrated high specificity and sensitivity for metastatic recurrence. ctDNA detection in the neoadjuvant setting indicated poor prognosis, highlighting its potential role across breast cancer care.
