TY - JOUR
T1 - Cell-free DNA Concentration as a Biomarker of Response and Recurrence in HER2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy
AU - Magbanua, Mark Jesus M.
AU - Ahmed, Ziad
AU - Sayaman, Rosalyn W.
AU - Swigart, Lamorna Brown
AU - Hirst, Gillian L.
AU - Yau, Christina
AU - Wolf, Denise M.
AU - Li, Wen
AU - Delson, Amy L.
AU - Perlmutter, Jane
AU - Pohlmann, Paula
AU - Symmans, W. Fraser
AU - Yee, Douglas
AU - Hylton, Nola M.
AU - Esserman, Laura J.
AU - DeMichele, Angela M.
AU - Rugo, Hope S.
AU - van’t Veer, Laura J.
N1 - Publisher Copyright:
© 2024 American Association for Cancer Research.
PY - 2024/6/1
Y1 - 2024/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85195220465&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85195220465&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-23-2928
DO - 10.1158/1078-0432.CCR-23-2928
M3 - Article
C2 - 38470545
AN - SCOPUS:85195220465
SN - 1078-0432
VL - 30
SP - 2444
EP - 2451
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 11
ER -