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

• 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 - diagnosis; Breast Neoplasms - drug therapy; Cell-Free Nucleic Acids - blood; Circulating Tumor DNA - blood; Circulating Tumor DNA - genetics; Female; Humans; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local - blood; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - drug therapy; 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
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-23-2928

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.