Dr Rastogi on the Utility of Post-Neoadjuvant, Pre-Surgery ctDNA Status in TNBC

“In practice, MRD gives us a much more precise and personalized way to talk with our patients. Instead of just relying on clinical and pathological features at baseline, we can incorporate a dynamic and biological marker that works with us regarding how the body reacts as it receives treatment for breast cancer.”

Priya Rastogi, MD, an associate professor of medicine at the University of Pittsburgh School of Medicine, as well as a medical oncologist at the University of Pittsburgh Medical Center Hillman Cancer Center, discussed findings from a circulating tumor DNA (ctDNA) substudy of the phase 3 NSABP B-59/GBG 96-GeparDouze trial (NCT03281954) evaluating a whole-exome sequencing, tumor-informed ctDNA minimal residual disease (MRD) assay in patients with early triple-negative breast cancer (TNBC) who received neoadjuvant chemotherapy with or without atezolizumab (Tecentriq).

The analysis, findings from which were presented at the 2026 AACR Annual Meeting, assessed ctDNA at a novel time point: following the completion of neoadjuvant therapy but prior to surgery. This time point was distinct from the postsurgical time point reported at the 2025 San Antonio Breast Cancer Symposium (SABCS), Rastogi began. She reported that ctDNA detected before surgery was strongly associated with the presence of residual disease at the time of surgery. Among patients with detectable ctDNA after completing neoadjuvant therapy, the assay predicted a lack of pathologic complete response with an 85.7% positive predictive value (95% CI, 60.1%-96.0%), she stated. Rastogi further noted that ctDNA positivity at this time point was strongly associated with distant recurrence, consistent with the earlier SABCS 2025 findings despite the different assessment window.

Rastogi emphasized that MRD testing offers a more precise and personalized framework for patient counseling, supplementing baseline clinical and pathologic features with a dynamic, biological marker reflecting treatment response. For patients with MRD-positive disease, she explained, these results may open discussions regarding clinical trial enrollment or, as evidence matures, treatment intensification. Conversely, for patients with MRD-negative disease, the findings can provide reassurance of favorable outcomes and may help avoid overtreatment, Rastogi concluded.