Whole Exome Sequencing of ctDNA Informs Post-Neoadjuvant Therapy Options for Patients with Triple Negative Early Breast Cancer
An interview with:
Marija Balic MD PhD, Chief of Medical Breast Oncology, NSABP Foundation, Inc.; UPMC Hillman Cancer Center; University of Pittsburgh School of Medicine, Pittsburgh, PA
SAN DIEGO, USA—In patients with triple negative breast cancer whole exome testing for ctDNA positivity after neoadjuvant therapy (before surgery) was found to be highly predictive of early relapse. This was in a study from Pittsburgh in the USA, reported to the 2026 Annual Meeting of the American Association for Cancer Research.
First author Marija Balic MD PhD, Chief of Medical Breast Oncology at the NSABP Foundation, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, in Pittsburgh, explained to our reporter Peter Goodwin how this could predict treatment resistance and greatly help the choice of further therapy:
AUDIO JOURNAL OF ONCOLOGY: Marija Balic MD PhD
IN: [GOODWIN] “I am here at the American ….
OUT:…..of Oncology, I’m Peter Goodwin 10:30 secs
AACR 2026 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-study of the NSABP B-59/GBG-96-GeparDouze Trial
Presenter/Authors
Marija Balic1, Gong Tang2, Priya Rastogi1, Gregory Young3, Matthew Wallace3, Joshua Acosta4, Andreas Schneeweiss5, Christie J. Hilton6, Tanner J. Freeman7, Jiahe Li8, Carston Denkert9, Mattea Reinisch10, Melanie R. Palomares3, Bradley A. Arrick3, Matthew Petitt3, Sujatha Murali11, Jean-François Boileau12, Dominique Boudreau13, Peter J. Polewski14, Saima Hassan15, Jorge Garces16, Gina Costa17, Janine LoBello18, João Mouta19, Walter C. Darbonne20, Frederick L. Baehner3, Eleftherios P. Mamounas21, Norman Wolmark22, Sibylle Loible23, Charles E. Geyer24
1NSABP Foundation, Inc.; UPMC Hillman Cancer Center; University of Pittsburgh School of Medicine, Pittsburgh, PA,
2NRG Oncology Statistics and Data Management Center, and University of Pittsburgh School of Public Health, Department of Biostatistics and Health Data Science, Pittsburgh, PA,
3Exact Sciences Corporation, Redwood City, CA,
4NSABP Foundation, Inc, and Allegheny Health Network, Pittsburgh, PA,
5National Center for Tumor Diseases (NCT); Division Gynecologic Oncology, Heidelberg University Hospital and German Cancer Research Center, Heidelburg, Germany,
6NSABP Foundation, Inc., and Medical University of South Carolina, Charleston, SC,
7NSABP Foundation, Inc., and The Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA,
8NSABP Foundation, Inc (Conducted) / Eli Lilly and Company (Current), Pittsburgh, PA,
9German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg, Hessen, Germany; Institute of Pathology, Philipps-Universität Marburg and University Hospital Marburg, Marburg, Germany,
10Interdisciplinary Breast Unit, Kliniken Essen-Mitte, Essen, and Interdisciplinary Breast Center, University Medical Center Mannheim, Essen, Germany,
11Department of Oncology, Southern California Permanente Medical Group, San Marcos, CA,12Jewish General Hospital Segal Cancer Centre McGill University, Montréal, QC, Canada,
13Hôpital du Saint-Sacrement, Québec, QC, Canada,
14Aurora Cancer Care, Advocate Aurora Health, Department of Surgical Oncology,, Milwaukee, WI,
15Centre Hospitalier de l’Université de Montréal (CHUM) Department of Surgical Oncology; Centre de Recherche de CHUM; Université de Montréal, Montréal, QC, Canada,
16Exact Sciences, Redwood City, CA,
17Exact Sciences, La Jolla, CA,
18Exact Sciences, Phoenix, AZ,
19Roche Farmacêutica Química, Global Product Development Medical Affairs Oncology, Amadora, Portugal,
20US Medical Affairs Oncology, Genentech, Inc., Department of Translational Medicine-Oncology, South San Francisco, CA,
21AdventHealth Cancer Institute, Department of Surgical Oncology, Orlando, FL,
22NSABP, and The University of Pittsburgh School of Medicine; UPMC Hillman Cancer Center, Division of Surgical Oncology, Department of Surgery, Pittsburgh, PA,
23German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg, and Goethe University Frankfurt, Hessen, Germany,
24NSABP Foundation, and The University of Pittsburgh School of Medicine, UPMC Hillman Cancer Center, Department of Medicine, Pittsburgh, PA
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.
Marija Balic MD PhD, AACR 2026 Audio Journal of Oncology April 30, 2026
