Circulating tumour DNA outperforms clinical markers like pathological complete remission in predicting relapse after neoadjuvant therapy for early breast cancer. Elisa Agostinetto MD from Institut Jules Bordet presented this prospective pooled analysis from Belgium and Italy at EBCC 2026.
Circulating Tumor DNA Trumps Clinical Prognostic Markers After Neoadjuvant Therapy for Patients with Early Breast Cancer
An interview with:
Elisa Agostinetto MD, Institut Jules Bordet, Brussels, Belgium
BARCELONA, Spain—Among patients being treated with neoadjuvant therapy for their early breast cancers, circulating tumor DNA performed better as an independent prognostic marker for predicting relapse and disease progression than clinical markers such as pathological complete remission. This was according to prospective study data from Belgium and Italy reported at the 2026 European Breast Cancer Conference by Elisa Agostinetto MD, a medical oncologist from the Institut Jules Bordet in Brussels. She discussed her findings with Audio Journal of Oncology reporter, Peter Goodwin:
AUDIO J0URNAL OF ONCOLOGY: Elisa Agostinetto MD
IN: [GOODWIN] “I’m here at the ……
OUT: ……of Oncology, I’m Peter Goodwin 10:04secs
EBCC 2026:
Abstract no: 12
Circulating tumor DNA at completion of neoadjuvant therapy is an independent prognostic marker: an individual patient-level pooled analysis of two prospective studies
- Agostinetto1, V. Appierto2, P. Minicozzi3, C. Sotiriou1, F. Rothé1, E. Tamborini2, F. Lebrun4,
- Belfiore2, D. t’Kint4, L. De Cecco5, L. Buisseret4, M.C. De Santis6, A. Gombos4, G. Bianchi7,
- Aftimos4, P. Verderio3, D. Vincent4, G. Pruneri2, M. Ignatiadis4, S. Di Cosimo MD2
1Institut Jules Bordet- Université libre de Bruxelles ULB- Hôpital Universitaire de Bruxelles H.U.B, Breast Cancer Translational Research Laboratory, Brussels, Belgium
2Fondazione IRCCS Istituto Nazionale dei Tumori, Advanced Diagnostics, Milan, Italy
3Fondazione IRCCS Istituto Nazionale dei Tumori, Epidemiology and Data Science, Milan, Italy
4Institut Jules Bordet- Université libre de Bruxelles ULB- Hôpital Universitaire de Bruxelles H.U.B, Medical Oncology, Brussels, Belgium
5Fondazione IRCCS Istituto Nazionale dei Tumori, Experimental Oncology, Mian, Italy
6Fondazione IRCCS Istituto Nazionale dei Tumori, Radiation Oncology, Milan, Italy
7Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Oncology, Milan, Italy
Background:
Circulating tumor DNA (ctDNA) is a promising biomarker in early breast cancer. However, limited sample sizes in available clinical studies weaken neoadjuvant evidence.
Materials and methods: Data from two independent prospective observational studies, one at the Institut Jules Bordet (Brussels), and one at the Istituto Nazionale dei Tumori (Milan), were pooled at the individual patient level for joint analysis. In both studies, women with early breast cancer received neoadjuvant therapy and underwent primary tumor-informed ctDNA assays at predefined time points: baseline (before initiation of neoadjuvant therapy), end of neoadjuvant therapy before surgery (EoT), and during follow-up. Associations between ctDNA detection and clinico- pathological variables (age, tumor size [e.g. T ≤5 cm vs. >5 cm], hormone receptor status, HER2 status, and pathological complete response (pCR) were evaluated using χ2 or Wilcoxon tests, as appropriate. The effect of ctDNA on event-free survival (EFS) was analyzed by univariable and multivariable Cox proportional hazards models adjusted for relevant covariates. A two-sided p value< 0.05 was considered statistically significant.
Results:
A total of 81 patients were analyzed. Median age was 48 (range 27-75) years at diagnosis; most had T≤5 cm (72%), node positive (68%) and triple negative (60%) disease. Breast cancer events were 26 throughout a median follow-up of 7 years (IQR 5.3-8.8). ctDNA was detected in 31/54 (57.4%) plasma samples at baseline, and in 11/64 (17%) plasma samples at the EoT. The detection of ctDNA was significantly associated with hormone receptor-negative status both at baseline and at the EoT (p<0.05). No association with pCR was observed at any time point. Patients with baseline ctDNA detection showed a non significant trend toward worse EFS (HR 1.56, 95% CI 0.58-4.22). Notably, detection of ctDNA at the EoT predicted breast cancer events and remained independently associated with decreased EFS even after adjustment for all other clinicopathological variables including pCR (HR 3.58, 95% CI 1.33-9.60).
Conclusions:
This individual patient-level pooled analysis includes one of the largest numbers of events reported to date in the ctDNA literature. ctDNA predicted breast cancer relapse, particularly when detected at the end of treatment, supporting the use of ctDNA for post-neoadjuvant risk stratification and subsequent therapeutic strategies.