TY - JOUR
T1 - Clinical significance and biology of circulating tumor DNA in high-risk early-stage HER2-negative breast cancer receiving neoadjuvant chemotherapy
AU - Magbanua, Mark Jesus M.
AU - Brown Swigart, Lamorna
AU - Ahmed, Ziad
AU - Sayaman, Rosalyn W.
AU - Renner, Derrick
AU - Kalashnikova, Ekaterina
AU - Hirst, Gillian L.
AU - Yau, Christina
AU - Wolf, Denise M.
AU - Li, Wen
AU - Delson, Amy L.
AU - Asare, Smita
AU - Liu, Minetta C.
AU - Albain, Kathy
AU - Chien, A. Jo
AU - Forero-Torres, Andres
AU - Isaacs, Claudine
AU - Nanda, Rita
AU - Tripathy, Debu
AU - Rodriguez, Angel
AU - Sethi, Himanshu
AU - Aleshin, Alexey
AU - Rabinowitz, Matthew
AU - Perlmutter, Jane
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:
© 2023 The Author(s)
PY - 2023/6/12
Y1 - 2023/6/12
N2 - Circulating tumor DNA (ctDNA) analysis may improve early-stage breast cancer treatment via non-invasive tumor burden assessment. To investigate subtype-specific differences in the clinical significance and biology of ctDNA shedding, we perform serial personalized ctDNA analysis in hormone receptor (HR)-positive/HER2-negative breast cancer and triple-negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NAC) in the I-SPY2 trial. ctDNA positivity rates before, during, and after NAC are higher in TNBC than in HR-positive/HER2-negative breast cancer patients. Early clearance of ctDNA 3 weeks after treatment initiation predicts a favorable response to NAC in TNBC only. Whereas ctDNA positivity associates with reduced distant recurrence-free survival in both subtypes. Conversely, ctDNA negativity after NAC correlates with improved outcomes, even in patients with extensive residual cancer. Pretreatment tumor mRNA profiling reveals associations between ctDNA shedding and cell cycle and immune-associated signaling. On the basis of these findings, the I-SPY2 trial will prospectively test ctDNA for utility in redirecting therapy to improve response and prognosis.
AB - Circulating tumor DNA (ctDNA) analysis may improve early-stage breast cancer treatment via non-invasive tumor burden assessment. To investigate subtype-specific differences in the clinical significance and biology of ctDNA shedding, we perform serial personalized ctDNA analysis in hormone receptor (HR)-positive/HER2-negative breast cancer and triple-negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NAC) in the I-SPY2 trial. ctDNA positivity rates before, during, and after NAC are higher in TNBC than in HR-positive/HER2-negative breast cancer patients. Early clearance of ctDNA 3 weeks after treatment initiation predicts a favorable response to NAC in TNBC only. Whereas ctDNA positivity associates with reduced distant recurrence-free survival in both subtypes. Conversely, ctDNA negativity after NAC correlates with improved outcomes, even in patients with extensive residual cancer. Pretreatment tumor mRNA profiling reveals associations between ctDNA shedding and cell cycle and immune-associated signaling. On the basis of these findings, the I-SPY2 trial will prospectively test ctDNA for utility in redirecting therapy to improve response and prognosis.
KW - circulating tumor DNA
KW - gene expression
KW - neoadjuvant chemotherapy
KW - pathologic complete response
KW - receptor subtype
KW - residual cancer burden
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U2 - 10.1016/j.ccell.2023.04.008
DO - 10.1016/j.ccell.2023.04.008
M3 - Article
C2 - 37146605
AN - SCOPUS:85161486966
SN - 1535-6108
VL - 41
SP - 1091-1102.e4
JO - Cancer cell
JF - Cancer cell
IS - 6
ER -