Personalizing Posttreatment Care: Insights From DARE, LEADER , and Emerging MRD Trials

Several ongoing studies are exploring the use of ctDNA in the adjuvant setting to improve early detection of recurrence and guide treatment interventions. One trial investigated adding immunotherapy to patients with detectable ctDNA, but challenges arose due to concurrent metastatic disease at detection and assay sensitivity limitations, resulting in no significant benefit from the intervention. Other studies focused on tailoring therapy based on genomic alterations or using targeted agents such as PARP inhibitors to intervene early, but many were limited by small patient numbers or insufficient ctDNA positivity rates. Advances in assay sensitivity now allow for earlier detection of minimal residual disease with a lead time of up to 12 months, offering potential windows for timely therapeutic intervention depending on breast cancer subtype.

The choice between tumor-informed and tumor-agnostic ctDNA assays depends on clinical circumstances. Tumor-informed assays, which require available primary tumor tissue, provide personalized and highly specific monitoring. In contrast, tumor-agnostic assays are valuable when tissue is unavailable or limited, using standard panels or methylation profiling. The integration of ctDNA results into clinical decision-making is complex, as they often reveal occult metastatic disease and add a new dimension to risk assessment, complementing existing clinical tools and imaging studies.

Looking forward, several pivotal trials are underway to determine whether interventions based on ctDNA positivity can improve patient outcomes, particularly in hormone receptor–positive disease. These studies are testing strategies such as adding targeted therapies or switching endocrine treatments for patients who remain ctDNA positive after initial therapy. Although ctDNA’s prognostic value is nearly absolute in predicting recurrence, the critical question is whether therapeutic interception can convert this prognostic marker into a predictive tool that changes the disease course. Ongoing research aims to identify the most effective drugs and strategies for this promising approach to personalized breast cancer management.