1. Cell-free DNA Concentration as a Biomarker of Response and Recurrence in HER2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy.
- Author
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Magbanua MJM, Ahmed Z, Sayaman RW, Brown Swigart L, Hirst GL, Yau C, Wolf DM, Li W, Delson AL, Perlmutter J, Pohlmann P, Symmans WF, Yee D, Hylton NM, Esserman LJ, DeMichele AM, Rugo HS, and van 't Veer LJ
- Subjects
- Adult, Aged, Female, Humans, Middle Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Circulating Tumor DNA blood, Circulating Tumor DNA genetics, Prognosis, Receptor, ErbB-2 metabolism, Receptor, ErbB-2 genetics, Treatment Outcome, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms pathology, Triple Negative Breast Neoplasms blood, Triple Negative Breast Neoplasms mortality, Triple Negative Breast Neoplasms genetics, Biomarkers, Tumor blood, Breast Neoplasms blood, Breast Neoplasms diagnosis, Breast Neoplasms drug therapy, Cell-Free Nucleic Acids blood, Neoadjuvant Therapy, Neoplasm Recurrence, Local blood, Neoplasm Recurrence, Local diagnosis, Neoplasm Recurrence, Local drug therapy
- 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., (©2024 American Association for Cancer Research.)
- Published
- 2024
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