Clinical Significance and Biology of Circulating Tumor DNA in High-Risk Early-Stage HER2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy

Authors

Mark Jesus M Magbanua
Lamorna Brown Swigart
Ziad Ahmed
Rosalyn W Sayaman
Derrick Renner
Ekaterina Kalashnikova
Gillian L Hirst
Christina Yau
Denise M Wolf
Wen Li
Amy L Delson
Smita Asare
Minetta C Liu
Kathy Albain
A Jo Chien
Andres Forero-Torres
Claudine Isaacs
Rita Nanda
Debu Tripathy
Angel Rodriguez
Himanshu Sethi
Alexey Aleshin
Matthew Rabinowitz
Jane Perlmutter
W Fraser Symmans
Douglas Yee
Nola M Hylton
Laura J Esserman
Angela M DeMichele
Hope S Rugo
Laura J van 't Veer

Language

English

Publication Date

6-12-2023

Journal

Cancer Cell

DOI

10.1016/j.ccell.2023.04.008

PMID

37146605

PMCID

PMC10330514

PubMedCentral® Posted Date

6-12-2024

PubMedCentral® Full Text Version

Author MSS

Abstract

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.

Keywords

Humans, Female, Breast Neoplasms, Triple Negative Breast Neoplasms, Circulating Tumor DNA, Neoadjuvant Therapy, Clinical Relevance, Antineoplastic Combined Chemotherapy Protocols, Biology, Erb-b2 Receptor Tyrosine Kinases

Published Open-Access

yes

Recommended Citation

Magbanua, Mark Jesus M; Brown Swigart, Lamorna; Ahmed, Ziad; et al., "Clinical Significance and Biology of Circulating Tumor DNA in High-Risk Early-Stage HER2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy" (2023). Faculty, Staff and Student Publications. 6123.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6123