Predicting Response to Neoadjuvant Therapy in Patients With Early-Stage Breast Cancer Using Circulating Tumor DNA Testing
Year: 2026
Type: article
Study design: Observational Study
Abstract: PURPOSE Accurate prediction of response to neoadjuvant therapy (NAT) and appropriate risk-stratification of patients following NAT are significant challenges in the care for patients with early-stage breast cancer. We evaluated whether circulating tumor DNA (ctDNA) trends during NAT can be an early indicator of treatment response to inform risk stratification and future disease management in this disease setting. METHODS The prospective CIPHER study (ClinicalTrials.gov identifier: NCT05333874 ) recruited 37 patients with stage II to III triple-negative breast cancer (TNBC) or human epidermal growth factor receptor 2–positive (HER2+) breast cancer who received standard-of-care NAT. ctDNA was assessed using a personalized, tumor-informed test (Signatera) before treatment, every 3 weeks during NAT, and after surgery. RESULTS Of the 37 enrolled patients, 81.1% (30/37) had ctDNA tested at baseline and were eligible for analysis on the study. Baseline ctDNA levels did not vary significantly between patients with TNBC and HER2+ disease. Patients who achieved early ctDNA clearance during NAT were more likely to have a negative ctDNA result after surgery ( P = .0128). In multivariable analysis, pretreatment ctDNA levels >10 mean tumor molecules per mL (MTM/mL) were associated with significantly higher risk of molecular or clinical relapse compared with <10 MTM/mL (odds ratio, 14.2 [95% CI, 1.36 to 147.08]). Postoperative ctDNA testing prompted a change in disease management for 60% (3/5) of patients who had a positive ctDNA result after surgery. CONCLUSION In this study, ctDNA dynamics during NAT was associated with level of response as observed by pathologic evaluation and identified those patients who may be at increased risk of relapse after surgery. Future studies investigating the associations between during- and post-NAT ctDNA status and pathologic response will determine whether ctDNA trends can serve as an adjunct or potential surrogate for pathologic response.
Source: JCO oncology advances.
DOI: 10.1200/oa-26-00022
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7204092058