Abstract / Summary
Post-neoadjuvant circulating tumor DNA (ctDNA) has been investigated as a minimal residual disease (MRD) marker in stage I-III triple-negative breast cancer (TNBC), but landmark timing and assay approaches vary. To assess whether post-neoadjuvant and/or peri-operative ctDNA MRD positivity is associated with poorer recurrence-related outcomes in TNBC with residual invasive disease, with overall survival evaluated as a secondary outcome and the association between ctDNA and pathologic complete response (pCR) assessed exploratorily. PubMed/MEDLINE, Embase, Web of Science Core Collection, and Scopus were searched through January 15, 2026. Eligible studies enrolled adults with TNBC treated with neoadjuvant systemic therapy and surgery and reported post-neoadjuvant or peri-operative ctDNA with time-to-event outcomes; recurrence-related quantitative syntheses focused on residual invasive disease or extractable non-pCR/residual cancer burden (RCB) subgroups. Risk of bias was assessed using QUIPS. Random-effects meta-analysis was performed when studies were comparable; otherwise, findings were summarized narratively. Twenty-two studies were included. Four studies contributed to the primary meta-analysis. Post-treatment ctDNA positivity was associated with poorer recurrence-related outcomes (pooled hazard ratio 4.63, 95% CI 3.07-6.98; I²=0%), although this estimate should be interpreted cautiously given the small number of contributing studies. Overall survival could not be synthesized quantitatively. Two studies assessed the ctDNA-pCR association, but results were summarized narratively because TNBC-specific data were not extractable in one study. In TNBC patients with residual invasive disease or extractable non-pCR/RCB subgroup data after neoadjuvant therapy, post-neoadjuvant and peri-operative ctDNA MRD positivity is associated with poorer recurrence-related outcomes, supporting further standardized prospective evaluation.
Primary Source
Breast cancer research and treatment
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