2026-04-03
Breast cancer: circulating tumor DNA, a key biomarker to anticipate relapse
Oncology Medical Biology
By Elodie Vaz | Published on April 3, 2026 | 3 min read
Breast 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.
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.”
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.
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.
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.
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.
Breast 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.
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