Persistence of circulating tumor DNA in breast cancer patients during neoadjuvant treatment is a significant predictor of poor tumor response
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Purpose:Accurate assessment of response during neoadjuvant systemic treatment (NST) poses a major clinical challenge. Therefore, a minimally-invasive assessment of tumor response based on cell-free circulating tumor DNA (ctDNA) may be beneficial to guide treatment decisions.Experimental Design: We profiled 93 genes in tissue from 193 early breast cancer patients. Patient-specific assays were designed to track ctDNA during NST from 145 patients with available plasma. ctDNA presence and levels were correlated with complete pathological response (pCR) and residual cancer burden (RCB) as well as with clinicopathologic characteristics of the tumor to identify potential proxies for ctDNA release. Moreover, we tested the predictive value of driver events identified in the tumor.Results:At baseline, ctDNA could be detected in 63/145 (43.4%) patients and persisted in 25/63 (39.7%) patients at mid-therapy (MT) and 15/63 (23.8%) patients at the end of treatment. ctDNA detection at MT was significantly associated with higher RCB (OR 0.062, 95% CI 0.01-0.48, P=0.0077). Out of 31 patients with ... (Show More)
Study Datasets 2 datasets.
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Targeted next-generation sequencing (NGS) of 93 frequently mutated genes in breast cancer using the QIAseq Human Breast Cancer Targeted Panel (QIAGEN), which uses digital sequencing by incorporating unique molecular barcodes (UMI).
|Illumina MiSeq,NextSeq 550||187|
Paired end shallow whole genome sequencing (sWGS) data for the identification of genomewide somatic copy number alterations (SCNA) and the estimation of tumor fractions.
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