Presence of ctDNA Predicts Worse Outcomes in Early Breast Cancer

Blood sample
Blood sample
The presence of ctDNA, both at baseline and after treatment, was associated with worse survival outcomes.

The following article features coverage from the European Society of Medical Oncology (ESMO) Congress 2021. Click here to read more of MPR‘s conference coverage.

A meta-analysis suggests the presence of circulating tumor DNA (ctDNA), at baseline and after neoadjuvant chemotherapy (NACT), can predict worse survival outcomes in patients with early breast cancer. These findings were presented at the European Society for Medical Oncology (ESMO) Congress 2021.

Researchers analyzed 11 studies investigating ctDNA as a biomarker in patients with early breast cancer, 1 prospective, randomized trial; 6 prospective, observational trials; and 4 ancillary studies.    

One endpoint the researchers assessed was the effect of ctDNA — at baseline, after the first treatment cycle, and after NACT — on overall survival (OS) and relapse-free survival (RFS), which was defined as any type of relapse event (RFS, disease-free survival, event-free survival, or distant disease-free survival).

The researchers also assessed the odds ratio (OR) for pathologic complete response (pCR) depending on ctDNA at baseline, as well as the positive and negative predictive values of ctDNA for pCR.

There was no association between baseline ctDNA and pCR (OR, 0.93; 95% CI, 0.32-2.66), and the diagnostic accuracy of ctDNA for pCR was low. The positive predictive value was 0.24, and the negative predictive value was 0.65.

On the other hand, the presence of ctDNA at baseline was associated with worse RFS (hazard ratio [HR], 4.22; 95% CI, 1.29-13.8) and OS (HR, 19.1; 95% CI, 6.9-53).

Likewise, the presence of ctDNA after NACT was associated with worse RFS (HR, 5.67; 95% CI, 2.73-11.75) and OS (HR, 4; 95% CI, 1.9-8.42).

The researchers also performed a subgroup analysis of patients with triple-negative breast cancer. In this group, the presence of ctDNA after NACT and surgery was associated with worse RFS (HR, 3.46; 95% CI, 1.93-6.18).

“Shedding of ctDNA at baseline and persistence after NACT identifies a subset of patients with worse prognosis and warrants further investigation as [an] additional tool to select patients requiring treatment escalation either during NACT or adjuvant, or where de-escalation could be possible,” the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Gonzalez NS, Papakonstantinou A, Pimentel I, et al. Meta-analysis of the prognostic value of circulating tumor DNA (ctDNA) in patients (pts) with early breast cancer (EBC). Presented at: European Society for Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract 152P.

This article originally appeared on Cancer Therapy Advisor