A blood test measuring circulating tumor DNA (ctDNA) may help identify older women with breast cancer who can safely avoid surgery and rely on endocrine therapy alone, according to a prospective study.
The research, published in Clinical Cancer Research, evaluated 43 patients aged 70 years and older with estrogen receptor–positive breast cancer who chose primary endocrine therapy instead of surgery. Researchers found that ctDNA status closely tracked with imaging results, and persistent ctDNA after 6 months of therapy was associated with tumor progression. In contrast, no patients with negative ctDNA at baseline experienced progression, highlighting the assay’s potential as a rule-out tool for disease worsening.
The findings support ctDNA’s growing role as a minimally invasive biomarker that could inform treatment stratification. Performed through routine blood draws, ctDNA testing enables more frequent, decentralized monitoring, compared with imaging. In this study, samples were often collected from patients’ homes, demonstrating a practical pathway for integrating molecular diagnostics into community-based care.
The study also showed that pretreatment ctDNA positivity was strongly associated with progression risk, even after adjusting for clinical factors such as age, tumor stage, and proliferation index. This suggests ctDNA could complement traditional pathology markers by providing real-time insight into tumor dynamics and treatment response.
ctDNA-negative patients appeared unlikely to benefit from escalation to surgery or radiation, which are associated with morbidity in older populations. Conversely, persistent ctDNA positivity may flag patients who require more aggressive intervention despite endocrine therapy.
Further analyses identified immune-related tumor microenvironment features in ctDNA-positive progressing tumors, including macrophage populations that promote cancer cell growth. While exploratory, these findings support the biological relevance of ctDNA as a surrogate for active disease.
The authors note that the study is small and not yet practice-changing. However, it highlights how liquid biopsy approaches could refine decision-making in populations where treatment risks must be carefully balanced against benefit.
If validated in larger trials, ctDNA testing could shift breast cancer management toward more personalized, less invasive care pathways, with diagnostic laboratories playing a central role in ongoing disease monitoring and therapeutic guidance.
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