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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Breast Cancer | Research

Identification of mutation patterns and circulating tumour DNA-derived prognostic markers in advanced breast cancer patients

Authors: Hao Liao, Jiayang Zhang, Tiantian Zheng, Xiaoran Liu, Jianxin Zhong, Bin Shao, Xiaoxi Dong, Xiaohong Wang, Pan Du, Bonnie L. King, Shidong Jia, Jianjun Yu, Huiping Li

Published in: Journal of Translational Medicine | Issue 1/2022

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Abstract

Background

The correlations between circulating tumour DNA (ctDNA)-derived genomic markers and treatment response and survival outcome in Chinese patients with advanced breast cancer (ABC) have not been extensively characterized.

Methods

Blood samples from 141 ABC patients who underwent first-line standard treatment in Peking University Cancer Hospital were collected. A next-generation sequencing based liquid biopsy assay (PredicineCARE) was used to detect somatic mutations and copy number variations (CNVs) in ctDNA. A subset of matched blood samples and tumour tissue biopsies were compared to evaluate the concordance.

Results

Overall, TP53 (44.0%) and PIK3CA (28.4%) were the top two altered genes. Frequent CNVs included amplifications of ERBB2 (24.8%) and FGFR1 (8.5%) and deletions of CDKN2A (3.5%). PIK3CA/TP53 and FGFR1/2/3 variants were associated with drug resistance in hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-positive (HER2 +) patients. The comparison of genomic variants across matched tumour tissue and ctDNA samples revealed a moderate to high concordance that was gene dependent. Triple-negative breast cancer (TNBC) patients harbouring TP53 or PIK3CA alterations had a shorter overall survival than those without corresponding mutations (P = 0.03 and 0.008). A high ctDNA fraction was correlated with a shorter progression-free survival (PFS) (P = 0.005) in TNBC patients. High blood-based tumor mutation burden (bTMB) was associated with a shorter PFS for HER2 + and TNBC patients (P = 0.009 and 0.05). Moreover, disease monitoring revealed several acquired genomic variants such as ESR1 mutations, CDKN2A deletions, and FGFR1 amplifications.

Conclusions

This study revealed the molecular profiles of Chinese patients with ABC and the clinical validity of ctDNA-derived markers, including the ctDNA fraction and bTMB, for predicting treatment response, prognosis, and disease progression.
Trial registration: ClinicalTrials.gov ID: NCT03792529. Registered January 3rd 2019, https://​clinicaltrials.​gov/​ct2/​show/​NCT03792529.
Appendix
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Metadata
Title
Identification of mutation patterns and circulating tumour DNA-derived prognostic markers in advanced breast cancer patients
Authors
Hao Liao
Jiayang Zhang
Tiantian Zheng
Xiaoran Liu
Jianxin Zhong
Bin Shao
Xiaoxi Dong
Xiaohong Wang
Pan Du
Bonnie L. King
Shidong Jia
Jianjun Yu
Huiping Li
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03421-8

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