Plasma ctDNA Testing Predicts Breast Cancer Recurrence After Neoadjuvant Therapy

Accurate identification of breast cancer patients at risk of relapse after pre-surgery treatment is central to guiding adjuvant decisions, particularly in aggressive disease. Circulating fragments of tumor DNA in blood reflect minimal residual disease and tumor burden. However, evidence for their utility around neoadjuvant therapy has been limited by small cohorts. A new study shows that circulating tumor DNA measured after pre-surgery treatment predicts subsequent recurrence in early breast cancer.

At the 15th European Breast Cancer Conference 2026 in Barcelona on March 27, 2026, investigators from Institut Jules Bordet, in collaboration with Istituto Nazionale dei Tumori, presented findings from a study evaluating circulating tumor DNA (ctDNA) in plasma as a biomarker of relapse following neoadjuvant therapy. The analysis included the largest number of individual patient events reported to date for ctDNA in this setting. The results suggest that the timing of ctDNA assessment is a critical factor for effective risk stratification.

The team analyzed plasma at three time points: study entry before neoadjuvant therapy, completion of neoadjuvant therapy prior to surgery, and during follow-up. The pooled, observational evaluation comprised two prospective studies enrolling 81 patients with early breast cancer at the two centers in Brussels and Milan. Ages ranged from 27 to 75 years (median 48 years). Most tumors were under 5 cm with lymph node involvement; 60% were triple‑negative. Follow-up spanned a median of approximately seven years, during which 21 patients recurred; one patient died without recurrence and four died after recurrence.

Circulating tumor DNA was detected in 57% of baseline samples, falling to 17% at completion of neoadjuvant therapy. Baseline ctDNA positivity showed a non‑significant trend toward higher recurrence risk, whereas detection after neoadjuvant therapy was associated with a 3.5‑fold greater likelihood of recurrence, even after adjustment for tumor size, age, and hormone receptor status.

ctDNA also predicted outcomes in patients who achieved pathological complete response, and its presence at baseline and post‑therapy was significantly associated with hormone receptor–negative disease. The authors noted strengths including long follow‑up and consecutive patient inclusion across more than one cancer center, and emphasized that ctDNA‑guided decision-making should be tested prospectively.

“We know already that ctDNA has prognostic relevance, and its detection is consistently associated with a higher risk of recurrence and worse survival, often anticipating clinical relapse by months. It is good at reflecting minimal residual disease and tumour burden. However, until now there has been limited evidence about its usefulness in the neoadjuvant setting, mainly due to small numbers of patients in available clinical studies,” said Dr. Elisa Agostinetto, medical oncologist and researcher at the Institut Jules Bordet.

“The analysis presented today at EBCC15 adds to the growing evidence that ctDNA in breast cancer has prognostic relevance and can help us to choose the most appropriate treatment for individual patients. Clinical trials should investigate this further to see if treatment decisions guided by ctDNA results actually improve outcomes. We also need to know if the presence of ctDNA has the same implications across all the different sub-types of breast cancer,” stated Dr. Javier Cortés, chair of the EBCC15 national organizing committee and co-director of the International Breast Cancer Center (IBCC) in Barcelona and of IOB in Madrid.

Related Links
Istituto Nazionale dei Tumori
Institut Jules Bordet
International Breast Cancer Center (IBCC)