The Pathologic Response Evaluation and Detection in Circulating Tumor-DNA Study: Ultrasensitive Circulating Tumor-DNA Assessment of Breast Cancer Minimal Residual Disease

作者：N. Hunter, Heather A. Parsons, Leslie Cope, J. V. Canzoniero, Fabio C.P. Navarro, Sherif El-Refai, Jesus D. Anampa, Joseph A. Sparano, Mothaffar F. Rimawi, A. Storniolo, Candace Mainor, Rita Nanda, A. DeMichele, Gaorav P. Gupta, E Stringer-Reasor, F. Lynce, Erin F. Cobain, Shannon Puhalla, R. C. Jankowitz, Brent N. Rexer, I. Mayer, E. Shelley Hwang, Kimberly Blackwell, Walid El Ayass, Young Lee, Carol Tweed, Mary Wilkinson, Angela Pennisi, Bonnie Sun, Pamela A. Wright, Julie R. Gralow, Richard Chen, S. M. Boyle, Vered Stearns, Antonio C. Wolff, Ben Ho Park · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco-25-02934 · 被引用次数：8 · 研究领域：Cancer Genomics and Diagnostics、Cancer Cells and Metastasis、Breast Cancer Treatment Studies

PURPOSE Patients with stage II/III human epidermal growth factor receptor 2 (HER2)–positive or triple-negative breast cancer (TNBC) frequently receive neoadjuvant therapy (NAT). Although pathologic complete response (pCR) correlates with improved outcomes, many non-pCR patients have long-term survival. Circulating tumor-DNA (ctDNA) minimal residual disease (MRD) assessment may provide additional or superior risk stratification. METHODS Pathologic Response Evaluation and Detection in Circulating Tumor-DNA is a prospective, multicenter study evaluating ctDNA as a biomarker of treatment response using a tumor-informed, ultrasensitive (<100 parts per million) assay. The primary objective was to determine whether the negative predictive value (NPV) of post-NAT ctDNA for pCR was ≥90%. A prespecified secondary objective for the TNBC cohort was to assess associations between ctDNA and 5-year invasive disease-free survival (IDFS). ctDNA was evaluated at baseline, after NAT before surgery, and after surgery. RESULTS Of 227 enrolled patients, 220 were evaluable for pCR (48% HER2-positive; 52% TNBC) and 91 patients (41%) had pCR. The primary objective was not met. Although all patients with pCR were ctDNA-negative after NAT, 40% of non-pCR patients were also ctDNA-negative (NPV, 60% [95% CI, 0.50 to 0.69]). However, the prespecified secondary objective was met. Detectable ctDNA after NAT was prognostic for recurrence (hazard ratio [HR], 8.9 [95% CI, 2.4 to 33]; P = .001), independent ...