Prognostic significance of circulating tumor DNA in early breast cancer: a systematic review and meta-analysis.
Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker for monitoring minimal residual disease (MRD) and predicting recurrence in early-stage breast cancer (EBC). Despite growing interest, the prognostic impact of ctDNA detection in this setting remains to be fully elucidated.
A systematic review and meta-analysis were conducted on prospective studies assessing the association between ctDNA positivity and outcomes in early or locally advanced non-metastatic breast cancer. Databases including PubMed and the Cochrane Library were systematically searched. Studies were included if they reported hazard ratios (HRs) for disease-free survival (DFS) and/or overall survival (OS) according to ctDNA status. Pooled HRs were calculated using random-effects models; heterogeneity was evaluated with the I2 statistic.
Eighteen studies comprising 1670 patients were included. ctDNA positivity was significantly associated with shorter DFS (pooled HR 6.92, 95% CI 3.64-13.13; p < 0.0001; I2 = 79.7%). This association held across subtypes and timepoints, including post-surgical and longitudinal assessments. In the neoadjuvant setting, ctDNA positivity was associated with increased recurrence risk (HR 6.06, 95% CI 2.85-12.87; p < 0.0001), while in the adjuvant setting, it was an even stronger predictor of relapse (HR 14.76, 95% CI 1.11-197.02; p = 0.042). In a combined early-stage setting, ctDNA positivity correlated with significantly worse DFS (HR 6.55, 95% CI 1.41-30.39; p = 0.017). A non-significant trend was observed for worse OS (HR 3.91, 95% CI 0.78-19.72; p = 0.098).
ctDNA positivity is a robust prognostic biomarker for recurrence in early breast cancer. Its integration into post-treatment surveillance and interventional trials may enable risk-adapted strategies and early therapeutic intervention.
A systematic review and meta-analysis were conducted on prospective studies assessing the association between ctDNA positivity and outcomes in early or locally advanced non-metastatic breast cancer. Databases including PubMed and the Cochrane Library were systematically searched. Studies were included if they reported hazard ratios (HRs) for disease-free survival (DFS) and/or overall survival (OS) according to ctDNA status. Pooled HRs were calculated using random-effects models; heterogeneity was evaluated with the I2 statistic.
Eighteen studies comprising 1670 patients were included. ctDNA positivity was significantly associated with shorter DFS (pooled HR 6.92, 95% CI 3.64-13.13; p < 0.0001; I2 = 79.7%). This association held across subtypes and timepoints, including post-surgical and longitudinal assessments. In the neoadjuvant setting, ctDNA positivity was associated with increased recurrence risk (HR 6.06, 95% CI 2.85-12.87; p < 0.0001), while in the adjuvant setting, it was an even stronger predictor of relapse (HR 14.76, 95% CI 1.11-197.02; p = 0.042). In a combined early-stage setting, ctDNA positivity correlated with significantly worse DFS (HR 6.55, 95% CI 1.41-30.39; p = 0.017). A non-significant trend was observed for worse OS (HR 3.91, 95% CI 0.78-19.72; p = 0.098).
ctDNA positivity is a robust prognostic biomarker for recurrence in early breast cancer. Its integration into post-treatment surveillance and interventional trials may enable risk-adapted strategies and early therapeutic intervention.
Authors
Sisca Sisca, Polito Polito, Silletta Silletta, La Cesa La Cesa, Scafetta Scafetta, Donato Donato, Gullotta Gullotta, Guarino Guarino, Barnini Barnini, Speziale Speziale, Troiano Troiano, Foderaro Foderaro, Iuliani Iuliani, Simonetti Simonetti, Cavalieri Cavalieri, Calagna Calagna, Cortellini Cortellini, Vincenzi Vincenzi, Tonini Tonini, Pantano Pantano
View on Pubmed