Abstract CT013: Whole-exome sequencing tumor-informed circulating tumor DNA detection after completion of neoadjuvant treatment predicts non-pCR and distant recurrence in patients with early triple-negative breast cancer (TNBC) — Results from a sub-s

Abstract PURPOSE: Presence of circulating tumor DNA (ctDNA) is strongly associated with recurrence risk in early triple-negative breast cancer (TNBC). NSABP B-59/GBG-96-GeparDouze evaluated atezolizumab or placebo added to neoadjuvant therapy (NAT) and as adjuvant therapy in 1,550 patients with stage II/III TNBC. A prospective ctDNA sub-study collected serial blood during the first two years after randomization. In the recent 2025 San Antonio Breast Cancer Symposium, we presented the primary endpoint demonstrating that post-surgery ctDNA positivity was associated with an ∼30-fold higher risk of distant recurrence. Here, post- NAT correlation with pCR and distant recurrence is presented. METHODS: Blood was collected at baseline, at completion of NAT prior to surgery, 3-6 weeks post-surgery, and 12- and 24-months after randomization. Primary tumors were analyzed via whole-exome sequencing for variant discovery. For ctDNA detection, libraries containing 15-60 ng of cell-free DNA from plasma samples were hybridized to patient-specific probes to enrich variant-containing regions, then sequenced. The association of post-NAT ctDNA status with pathological complete response, pCR (ypT0/is, ypN0) status and distant recurrence-free interval (dRFI) was determined. Additionally, baseline plasma ctDNA concentration was analyzed by T stage and nodal status RESULTS: At baseline, ctDNA was detected in 153 of 160 patients (96%). ctDNA was detected in 14 of 155 (9%) patients after completion of NAT. Positive ctDNA status after NAT was associated with residual invasive disease at surgery, and positive predictive value for non-pCR was 85.7%. Among the 97 patients with pCR after NAT, 95 (97.9%) were ctDNA-negative prior to surgery. Post-NAT pre-surgery ctDNA status was strongly associated with dRFI, with an HR 10.2 (3.8- 27.3; p<0.0001). Baseline plasma ctDNA concentration significantly increased by T stage (p<0.0001) and nodal status (p=0.0146). CONCLUSIONS: Building on our prior findings, post-NAT, pre-surgery ctDNA-positivity was strongly associated with inferior dRFI, mirroring the negative prognostic impact previously observed for post-surgery ctDNA. Moreover, post-NAT ctDNA positivity showed a high positive predictive value for non-pCR, highlighting its potential utility as an early indicator of treatment resistance and risk stratification. Citation Format: Marija Balic, Gong Tang, Priya Rastogi, Gregory Young, Matthew Wallace, Joshua Acosta, Andreas Schneeweiss, Christie J. Hilton, Tanner J. Freeman, Jiahe Li, Carston Denkert, Mattea Reinisch, Melanie R. Palomares, Bradley A. Arrick, Matthew Petitt, Sujatha Murali, Jean-François Boileau, Dominique Boudreau, Peter J. Polewski, Saima Hassan, Jorge Garces, Gina Costa, Janine LoBello, João Mouta, Walter C. Darbonne, Frederick L. Baehner, Eleftherios P. Mamounas, Norman Wolmark, Sibylle Loible, Charles E. Geyer. Whole-exome sequencing tumor-informed circulating tumor DNA detection after completion of neoadjuvant treatment predicts non-pCR and distant recurrence in patients with early triple-negative breast cancer (TNBC) — Results from a sub-study of the NSABP B-59/GBG-96-GeparDouze Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT013.