Cell-free DNA Concentration as a Biomarker of Response and Recurrence in HER2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy

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 fro...

Full description

Saved in:
Bibliographic Details
Published in:Clinical cancer research 2024-06, Vol.30 (11), p.2444-OF8
Main Authors: Magbanua, Mark Jesus M, Ahmed, Ziad, Sayaman, Rosalyn W, Brown Swigart, Lamorna, Hirst, Gillian L, Yau, Christina, Wolf, Denise M, Li, Wen, Delson, Amy L, Perlmutter, Jane, Pohlmann, Paula, Symmans, W Fraser, Yee, Douglas, Hylton, Nola M, Esserman, Laura J, DeMichele, Angela M, Rugo, Hope S, van 't Veer, Laura J
Format: Article
Language:English
Subjects:
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biomarkers, Tumor - blood
Breast Neoplasms - blood
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - mortality
Breast Neoplasms - pathology
Cell-Free Nucleic Acids - blood
Circulating Tumor DNA - blood
Circulating Tumor DNA - genetics
Female
Humans
Middle Aged
Neoadjuvant Therapy - methods
Neoplasm Recurrence, Local - blood
Neoplasm Recurrence, Local - drug therapy
Neoplasm Recurrence, Local - genetics
Neoplasm Recurrence, Local - pathology
Prognosis
Receptor, ErbB-2 - genetics
Receptor, ErbB-2 - metabolism
Treatment Outcome
Triple Negative Breast Neoplasms - blood
Triple Negative Breast Neoplasms - drug therapy
Triple Negative Breast Neoplasms - genetics
Triple Negative Breast Neoplasms - mortality
Triple Negative Breast Neoplasms - pathology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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. 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. 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.
ISSN:1078-0432
1557-3265
1557-3265
DOI:10.1158/1078-0432.CCR-23-2928