By Elodie Vaz | Published on April 3, 2026 | 3 min readBreast cancer
remains the most common cancer among women worldwide. Despite major therapeutic
advances, particularly in early-stage disease, the risk of recurrence remains a
central challenge in patient management. This risk varies according to tumor
subtypes, especially in aggressive forms such as triple-negative or hormone
receptor-negative (HR−) cancers, which are often less responsive to
conventional treatments.
In this context,
neoadjuvant strategies—such as chemotherapy, radiotherapy, or hormone therapy
administered before surgery—help reduce tumor size and assess treatment
response. However, even when an apparent response is achieved, some patients
later experience relapse, reflecting the persistence of minimal residual
disease that is difficult to detect.
Assessing the
prognostic value of circulating tumor DNA
Presented at the
15th European Breast Cancer Conference, this study aimed to evaluate the
ability of circulating tumor DNA (ctDNA) to predict the risk of recurrence
after neoadjuvant treatment.
ctDNA consists of
fragments of DNA released from tumor cells into the bloodstream. While already
recognized as a prognostic biomarker in several oncological settings, its
specific utility after preoperative treatment had remained poorly documented
due to limited patient numbers in previous studies.
As Professor Elisa
Agostinetto, oncologist at the Jules Bordet Institute, explains: “We already
know that circulating tumor DNA (ctDNA) has prognostic value […] However, until
now, data regarding its usefulness in the neoadjuvant setting were limited.”
A longitudinal
real-world analysis
Researchers analyzed
plasma samples from 81 patients with early-stage breast cancer, enrolled in two
prospective studies conducted in collaboration with the Istituto Nazionale dei
Tumori in Milan.
ctDNA samples were
collected at three key time points: before the start of neoadjuvant treatment,
after its completion and before surgery, and during follow-up, with a median
duration of approximately seven years.
The study
population, aged 27 to 75 years (median 48), mostly had tumors smaller than 5
cm with lymph node involvement. Nearly 60% had triple-negative breast cancer.
During follow-up, 21
patients experienced recurrence and four died as a result, providing a
relatively high number of events for this type of analysis.
A stronger
prognostic signal after treatment
The results show
that the presence of ctDNA is strongly associated with relapse risk,
particularly when detected after neoadjuvant therapy.
While 57% of
patients had detectable ctDNA at baseline, this proportion dropped to 17% after
treatment. Baseline ctDNA was associated with a trend toward recurrence but did
not reach statistical significance. In contrast, ctDNA detection after
neoadjuvant therapy was associated with a 3.5-fold increased risk of relapse,
independent of conventional clinical factors.
Even among patients
who achieved a pathological complete response, ctDNA retained predictive value,
suggesting it accurately reflects minimal residual disease. “The results […]
showed that the presence of circulating tumor DNA (ctDNA) was associated with
an increased risk of breast cancer recurrence, particularly when ctDNA was
detected at the end of preoperative treatment,” notes Professor Elisa
Agostinetto.
“These findings suggest that ctDNA could help identify patients at
higher risk […] and guide additional treatment if needed,” she adds.
Toward more
personalized medicine
Based on a long-term
cohort with a substantial number of events, this study reinforces the role of
ctDNA as a dynamic biomarker of recurrence risk. It suggests that a simple
blood test performed after neoadjuvant treatment could help guide postoperative
therapeutic decisions.
However, its
integration into routine clinical practice still requires prospective
validation. “At present, it is not used in routine clinical practice […]”
reminds Professor Elisa Agostinetto, who calls for trials in which treatment
decisions are directly guided by this biomarker.
According to
independent expert Javier Cortés, “this analysis […] further supports the
evidence […] that circulating tumor DNA (ctDNA) […] can help us choose the most
appropriate treatment for each patient.”
The next step will
be to demonstrate that early intervention in ctDNA-positive patients can
effectively improve outcomes. Beyond breast cancer, this approach could reshape
oncological follow-up by incorporating circulating biomarkers capable of
detecting the earliest signs of relapse well before clinical symptoms appear.
Read next: Breast cancer: shorter radiotherapy becomes the new global standard
About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on human life. A registered nurse since 2010, she spent twelve years at patients’ bedsides before exchanging her stethoscope for a notebook. She now investigates the links between environment and health, convinced that the vitality of life cannot be reduced to that of humans alone.
