Circulating Tumor DNA After Neoadjuvant Therapy Predicts Breast Cancer Recurrence

Advances in liquid biopsy technologies are dramatically changing how clinicians evaluate the presence of residual disease and the risk of cancer recurrence in patients with breast cancer. Recent data indicate that circulating tumor DNA (ctDNA)—tumor-derived genetic material detectable in blood—may be an excellent biomarker for identifying patients at risk of relapse, especially when the measurement is taken after neoadjuvant (presurgical) therapy. New data presented at the 2026 European Breast Cancer Conference showcase the increasing application of ctDNA for determining patient management after treatment and improving long-term outcomes.¹

ctDNA as a Marker of Minimal Residual Disease

Breast cancer recurrence remains a significant clinical challenge, even among patients who achieve favorable responses to therapy. Although existing prognostic markers, such as pathologic complete response (pCR), are valuable for predicting relapse, they provide only partial insight. ctDNA, by contrast, enables more detailed, real-time monitoring of minimal residual disease.²

In the recent prospective study led by Elisa Agostinetto, MD, medical oncologist at Institut Jules Bordet, investigators evaluated ctDNA levels at multiple time points, including baseline, after neoadjuvant therapy, and prior to surgery. The presence of ctDNA following presurgical treatment was strongly associated with an increased likelihood of disease recurrence.¹

“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 presurgery treatment,” Agostinetto noted. “These results suggest that ctDNA could be useful in identifying patients at higher risk after neoadjuvant therapy and in guiding additional treatment if needed.”¹

This reinforces the concept that ctDNA reflects ongoing tumor activity that may not be captured by imaging or pathology alone.

Superior Predictive Value Compared With Traditional Measures

Conventional markers in predicting outcomes may be outperformed by ctDNA. One study published in collaboration with the American Association for Cancer Research found that those patients with measurable ctDNA following the neoadjuvant treatment had a far poorer prognosis compared with those without ctDNA. Even among patients who achieved pCR and had detectable ctDNA, survival was drastically reduced.²

Further research has supported these findings, indicating that post–neoadjuvant treatment ctDNA positivity is a very strong indicator of relapse in all breast cancer subtypes.³ In some groups, individuals found to have ctDNA prior to surgery were at significantly higher risk of relapse, which further confirms the prognostic importance of this marker.⁴

Clinical Implications for Treatment Stratification

The integration of ctDNA into clinical practice could significantly impact how oncologists customize therapy. By using ctDNA testing to identify patients likely to have a recurrence, they can be treated earlier with additional or alternative adjuvant therapies. Conversely, patients who have no ctDNA detected may not need treatment changes, therefore lessening exposure to harmful adverse effects and enhancing the overall quality of life.

“We know already that ctDNA has prognostic relevance, and its detection is consistently associated with a higher risk of recurrence and a worse survival, often anticipating clinical relapse by months. It is good at reflecting minimal residual disease and tumor burden. However, until now, there has been limited evidence about its usefulness in the neoadjuvant setting, mainly due to the small numbers of patients in available clinical studies. Our analysis includes the largest number of events following neoadjuvant treatment and shows that ctDNA can be useful in guiding further treatments. At present, it is not used as a standard clinical practice for prognosis outside of clinical trials,” said Agostinetto.

Future Directions and Ongoing Challenges

Despite its potential, several issues need to be resolved before ctDNA is routinely integrated into breast cancer management. Differences in assay sensitivity, sample collection timing, and result interpretation are still being explored. Prospective clinical trials are needed to determine whether ctDNA-guided treatment strategies translate into improved survival outcomes.

On the other hand, emerging data indicate that ctDNA is a revolutionary tool in cancer treatment. By facilitating early identification of leftover cancer cells and providing accurate risk assessment, ctDNA could drastically change how patients with breast cancer are monitored and treated after therapy. As studies progress, pharmacists, along with other cancer care providers, will be indispensable in understanding these results and applying them in a patient-centered manner.

REFERENCES

1. Tumor DNA circulating in patients’ blood after presurgery treatments predicts whether breast cancer will return. News release. European Organisation for Research and Treatment of Cancer. March 26, 2026. Accessed April 1, 2026. https://www.eurekalert.org/news-releases/1121015

2. ctDNA levels after neoadjuvant therapy may predict breast cancer recurrence better than pathologic complete response. News release. American Association for Cancer Research. January 14, 2026. Accessed April 1, 2026. https://www.eurekalert.org/news-releases/1112717

3. Lin PH, Wang MY, Lo C, et al. Circulating tumor DNA as a predictive marker of recurrence for patients with stage II-III breast cancer treated with neoadjuvant therapy. Front Oncol. 2021;11:736769. doi:10.3389/fonc.2021.736769

4. Hunter N, Parsons HA, Cope L, et al. Circulating tumor DNA, pathologic response after neoadjuvant therapy, and survival: first results from TBCRC 040 (the PREDICT-DNA trial). J Clin Oncol. 2025;43(suppl 16):1009. doi:10.1200/JCO.2025.43.16_suppl.1009