Impact of ctDNA Positivity on Early Breast Cancer Outcomes Explored

A recent real-world analysis presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting has revealed a significant correlation between circulating tumor DNA (ctDNA) positivity and poorer outcomes in patients with early-stage breast cancer. The study, which utilized data from the Flatiron Health Research Database, demonstrated that patients testing positive for ctDNA exhibited a higher risk of recurrence and reduced overall survival, irrespective of breast cancer subtypes.

The analysis included data from 4,639 patients diagnosed with early-stage breast cancer who underwent at least one ctDNA test between January 1, 2018, and August 31, 2024. Among these, 921 patients (19.9%) tested positive for ctDNA. Notably, the median age of these patients was 58 years, compared to 64 years for those with negative ctDNA results. Testing was predominantly conducted in the adjuvant setting, with a significant emphasis on patients diagnosed with stage I (43.3%) and stage II (37.1%) disease. The overall survival (OS) probability for ctDNA-positive patients was reported at 85% over five years, contrasting starkly with 98% for those who tested negative.

According to Erin Fidyk, ANP-BC, MBA, senior clinical director of Oncology at Flatiron Health and lead author of the study, the findings suggest that ctDNA testing could play a crucial role in refining risk stratification and personalizing treatment plans for breast cancer patients. Fidyk emphasized, "Clinical integration opportunities include using ctDNA to identify patients who may benefit from escalated therapies."

The study also highlighted a marked increase in the adoption of ctDNA testing, rising from 1.6% of eligible patients in 2020 to 4.25% in 2023. This escalation was particularly pronounced among hormone receptor-negative/HER2-negative patients, where testing prevalence reached 4.9%. The study's retrospective design, however, has limitations, including potential selection biases and a lack of generalizability across diverse clinical settings.

Dr. Sarah Johnson, Professor of Oncology at Johns Hopkins University, noted, "The results of this study strongly advocate for the incorporation of ctDNA testing into routine clinical practice, as it provides essential prognostic information that could significantly influence treatment decisions."

The study's authors acknowledged that further research is necessary, including longer follow-up periods and prospective validation of ctDNA's prognostic value in larger clinical trials. They also pointed out that the clinical rationale for ctDNA testing—whether for routine surveillance or symptom-driven use—was not captured in this analysis, which could affect interpretation of the results.

In summary, this significant real-world analysis indicates that ctDNA positivity is a reliable marker for predicting worse outcomes in early-stage breast cancer patients. As the medical community continues to explore the implications of this testing, it holds promise for enhancing personalized treatment approaches and improving patient outcomes in the future.