Faculty, Staff and Student Publications

Language

English

Publication Date

6-3-2024

Journal

Clinical Cancer Research

DOI

10.1158/1078-0432.CCR-23-2928

PMID

38470545

PMCID

PMC11147708

PubMedCentral® Posted Date

12-3-2024

PubMedCentral® Full Text Version

Author MSS

Abstract

Purpose: We previously demonstrated the clinical significance of circulating tumor DNA (ctDNA) in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy (NAC). Here, we compared its predictive and prognostic value with cell-free DNA (cfDNA) concentration measured in the same samples from the same patients.

Experimental design: 145 patients with hormone receptor (HR)-positive/HER2-negative and 138 triple-negative breast cancer (TNBC) with ctDNA data from a previous study were included in the analysis. Associations of serial cfDNA concentration with residual cancer burden (RCB) and distant recurrence-free survival (DRFS) were examined.

Results: In TNBC, we observed a modest negative correlation between cfDNA concentration 3 weeks after treatment initiation and RCB, but none of the other timepoints showed significant correlation. In contrast, ctDNA was significantly positively correlated with RCB at all timepoints (all R > 0.3 and P < 0.05). In the HR-positive/HER2-negative group, cfDNA concentration did not associate with response to NAC, but survival analysis showed that high cfDNA shedders at pretreatment had a significantly worse DRFS than low shedders (hazard ratio, 2.12; P = 0.037). In TNBC, the difference in survival between high versus low cfDNA shedders at all timepoints was not statistically significant. In contrast, as previously reported, ctDNA at all timepoints was significantly correlated with DRFS in both subtypes.

Conclusions: In TNBC, cfDNA concentrations during therapy were not strongly correlated with response or prognosis. In the HR-positive/HER2-negative group, pretreatment cfDNA concentration was prognostic for DRFS. Overall, the predictive and prognostic value of cfDNA concentration was more limited than that of ctDNA.

Keywords

Adult, Aged, Female, Humans, Middle Aged, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Breast Neoplasms, Cell-Free Nucleic Acids, Circulating Tumor DNA, Neoadjuvant Therapy, Neoplasm Recurrence, Local, Prognosis, Erb-b2 Receptor Tyrosine Kinases, Treatment Outcome, Triple Negative Breast Neoplasms

Published Open-Access

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