Open AccessCirculating tumor DNA shows variable clonal response of breast cancer during neoadjuvant chemotherapy
Author(s) -
Jiyeon Kim,
Donghyun Park,
DaeSoon Son,
Seok Jin Nam,
Seok Won Kim,
Hae Hyun Jung,
Yeon Jeong Kim,
Gahee Park,
Woong-Yang Park,
Jeong Eon Lee,
Yeon Hee Park
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.21198
Subject(s) - breast cancer , digital polymerase chain reaction , medicine , chemotherapy , cancer , cancer research , somatic cell , circulating tumor dna , oncology , primary tumor , germline , gene , biology , polymerase chain reaction , genetics , metastasis
Circulating tumor DNA (ctDNA) correlates with tumor burden and provides early detection of treatment response and tumor genetic alterations in breast cancer (BC). In this study, we aimed to identify genetic alterations during the process of tumor clonal evolution and examine if ctDNA level well indicated clinical response to neoadjuvant chemotherapy (NAC) and BC recurrence. We performed targeted ultra-deep sequencing of plasma DNAs, matched germline DNAs and tumor DNAs from locally advanced BC patients. Serial plasma DNAs were collected at diagnosis, after the 1 st cycle of NAC and after curative surgery. For the target enrichment, we designed RNA baits covering a total of ∼202kb regions of the human genome including a total of 82 cancer-related genes. For ctDNA, 15 serial samples were collected and 87% of plasma SNVs were detected in 13 BC samples that had somatic alterations in tumor tissues. The TP53 mutation was most commonly detected in primary tumor tissues and plasma followed by BRCA1 and BRCA2 . At BC diagnosis, the amount of plasma SNVs did not correlate with clinical stage at diagnosis. With respect to the therapeutic effects of NAC, we found two samples in which ctDNA disappeared after the 1 st NAC cycle achieved a pathologic complete response (pCR). In addition, the amount of ctDNA correlated with residual cancer volume detected by breast MRI. This targeted ultra-deep sequencing for ctDNA analysis would be useful for monitoring tumor burden and drug resistance. Most of all, we suggest that ctDNA could be the earliest predictor of NAC response.