Fragments of tumor DNA circulating in the blood can predict the likelihood of breast cancer returning, especially when samples are collected after patients have completed treatments before surgery, according to research presented at the 15th European Breast Cancer Conference (EBCC15) in Barcelona on Mar. 26.
This finding is important because it could help doctors assess a patient's risk of relapse and plan personalized treatments following surgery. By analyzing circulating tumor DNA (ctDNA) after neoadjuvant therapy—which includes chemotherapy, radiotherapy, or hormone therapy given before surgery—doctors may better identify those who need additional care.
Dr Elisa Agostinetto, a medical oncologist and researcher at Institut Jules Bordet in Brussels, led a team that analyzed ctDNA in blood plasma from 81 women with early breast cancer enrolled in two studies. The study included patients aged between 27 and 75 years old; most had tumors smaller than five centimeters that had spread to lymph nodes. Over half had triple negative breast cancer—a type more common among younger women and less responsive to treatment.
Samples were taken at three points: before starting neoadjuvant treatment, at the end of this treatment but before surgery, and during follow-up (median follow-up was about seven years). During this period, one patient died without recurrence; twenty-one experienced recurrence; four died after recurrence. Dr Agostinetto said: "The results from this large, prospective study, conducted in a real-world setting, showed that finding ctDNA was linked to a higher chance of breast cancer coming back, especially when ctDNA was detected at the end of pre-surgery treatment. These results suggest that ctDNA could be useful in identifying patients at higher risk after neoadjuvant therapy, and to guide additional treatment if needed."
The researchers found ctDNA present in over half the samples before treatment began but only in 17% after completing neoadjuvant therapy. Patients with detectable ctDNA post-treatment were found to be three-and-a-half times more likely to experience recurrence during follow-up—even when accounting for factors like age or tumor size. Notably, even those whose tumors appeared gone after initial therapies still faced higher risks if their blood contained ctDNA.
The presence of ctDNA correlated significantly with hormone receptor negative disease—a form often harder to treat successfully—at both baseline and post-treatment stages. Dr Agostinetto said: "We know already that ctDNA has prognostic relevance... However, until now there has been limited evidence about its usefulness in the neoadjuvant setting... Our analysis includes the largest number of events following neoadjuvant treatment... At present it is not used as standard clinical practice for prognosis outside clinical trials." She called for further prospective trials where treatments are guided by ctDNA findings.
Dr Javier Cortés—chair of EBCC15's organizing committee who was not involved with the research—noted: "The analysis presented today at EBCC15 adds to the growing evidence that ctDNA in breast cancer has prognostic relevance and can help us choose the most appropriate treatment for individual patients... We also need to know if presence of ctDNA has same implications across all different sub-types."
