Identification of mutation patterns and circulating tumour DNA-derived prognostic markers in advanced breast cancer patients.
J Transl Med
; 20(1): 211, 2022 05 13.
Article
em En
| MEDLINE
| ID: mdl-35562750
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 .Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Neoplasias de Mama Triplo Negativas
/
DNA Tumoral Circulante
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
J Transl Med
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China