scholarly journals Association of a novel circulating tumor DNA next-generating sequencing platform with circulating tumor cells (CTCs) and CTC clusters in metastatic breast cancer

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrew A. Davis ◽  
Qiang Zhang ◽  
Lorenzo Gerratana ◽  
Ami N. Shah ◽  
Youbin Zhan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Genomic Alteration ◽  
Genomic Alterations ◽  
Disease Heterogeneity ◽  
Tumor Dna

Abstract Purpose Liquid biopsies, including circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), can be used to understand disease prognosis, tumor heterogeneity, and dynamic response to treatment in metastatic breast cancer (MBC). We explored a novel, 180-gene ctDNA panel and the association of this platform with CTCs and CTC clusters. Methods A total of 40 samples from 22 patients with MBC were included in the study. For the primary analysis, all patients had ctDNA sequencing using the PredicinePLUS™ platform. CTCs and CTC clusters were examined using the CellSearch™ System. Clinical and pathological variables were reported using descriptive analyses. Associations between CTC count and specific genomic alterations were tested using the Mann-Whitney U test. Results Of 43 sequenced patients, 40 (93%) had at least one detectable genomic alteration with a median of 6 (range 1–22). Fifty-seven different genes were altered, and the landscape of genomic alterations was representative of MBC, including the commonly encountered alterations TP53, PTEN, PIK3CA, ATM, BRCA1, CCND1, ESR1, and MYC. In patients with predominantly hormone-receptor-positive MBC, the number of CTCs was significantly associated with alterations in ESR1 (P < 0.005), GATA3 (P < 0.05), CDH1 (P < 0.0005), and CCND1 (P < 0.05) (Mann-Whitney U test). Thirty-six percent of patients had CTC clusters, which were associated with alterations in CDH1, CCND1, and BRCA1 (all P < 0.05, Mann-Whitney U test). In an independent validation cohort, CTC enumeration confirmed significant associations with ESR1 and GATA3, while CTC clusters were significantly associated with CDH1. Conclusions We report on a novel ctDNA platform that detected genomic alterations in the vast majority of tested patients, further indicating potential clinical utility for capturing disease heterogeneity and for disease monitoring. Detection of CTCs and CTC clusters was associated with particular genomic profiles.

Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) longitudinal monitoring of metastatic breast cancer (MBC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e23030-e23030
Author(s):  
Ricardo Lima Barros Costa ◽  
Giovanna Rossi ◽  
Zhaomei Mu ◽  
Laura Katherine Austin ◽  
Alfred Rademaker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Tumor Dna

scholarly journals Liquid Biopsy in Metastatic Breast Cancer: Current Role of Circulating Tumor Cells and Circulating Tumor DNA

2021 ◽  
Author(s):  
Maggie Banys-Paluchowski ◽  
Tanja N. Fehm ◽  
Donata Grimm-Glang ◽  
Achim Rody ◽  
Natalia Krawczyk
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Therapy Monitoring ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Her2 Positive ◽  
Tumor Dna

Background In metastatic breast cancer, blood-based diagnostics have become a major focus of oncological research in the last two decades. Detection of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) has the potential to improve prognosis assessment and complement standard therapy monitoring tools. Summary To date, several large analyses have confirmed high CTC counts as an independent prognostic factor. Persistently high CTC numbers during systemic treatment are associated with early progression but it remains to be clarified which therapeutic options should be offered to such patients since the SWOG 0500 trial failed to show benefit from early switch to another chemotherapy regimen in patients with CTC persistence. In comparison, evidence on the prognostic value of ctDNA is still limited. Most importantly, liquid biopsy-guided treatment interventions have been investigated in several trials. In patients with hormone receptor positive HER2 negative metastatic breast cancer CTC-driven therapy choices resulted in similar PFS to physician’s choice treatment. Recently, the DETECT III trial has shown that patients with HER2 negative metastatic breast cancer and HER2 positive CTCs may benefit from targeted anti-HER2 treatment with lapatinib. ctDNA-driven therapy selection has already been approved in clinical routine: alpelisib is the first targeted treatment indicated on the basis of a ctDNA test. Key messages CTCs and ctDNA predict clinical outcome and have a potential to improve therapy choices in metastatic breast cancer.

scholarly journals Longitudinal Dynamics of Circulating Tumor Cells and Circulating Tumor DNA for Treatment Monitoring in Metastatic Breast Cancer

2021 ◽  
pp. 943-952
Author(s):  
Lorenzo Gerratana ◽  
Andrew A. Davis ◽  
Qiang Zhang ◽  
Debora Basile ◽  
Giovanna Rossi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Prospective Cohort ◽  
Retrospective Cohort ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Wilcoxon Test ◽  
Tumor Dna

PURPOSE Liquid biopsy–based biomarkers, including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), are increasingly important for the characterization of metastatic breast cancer (MBC). The aim of the study was to explore CTCs and ctDNA dynamics to better understand their potentially complementary role in describing MBC. METHODS The study retrospectively analyzed 107 patients with MBC characterized with paired CTCs and ctDNA assessments and a second prospective cohort, which enrolled 48 patients with MBC. CTCs were immunomagnetically isolated and ctDNA was quantified and then characterized through next-generation sequencing in the retrospective cohort and droplet digital polymerase chain reaction in the prospective cohort. Matched pairs variations at baseline, at evaluation one (EV1), and at progression were tested through the Wilcoxon test. The prognostic role of ctDNA parameters was also investigated. RESULTS Mutant allele frequency (MAF) had a significant decrease between baseline and EV1 and a significant increase between EV1 and progression. Number of detected alterations steadily increased across timepoints, CTCs enumeration (nCTCs) significantly increased only between EV1 and progression. MAF dynamics across the main altered genes was then investigated. Plasma DNA yield did not vary across timepoints both in the retrospective cohort and in the prospective cohort, while the short fragments fraction showed a potential role as a prognostic biomarker. CONCLUSION nCTCs and ctDNA provide complementary information about prognosis and treatment benefit. Although nCTCs appeared to assess tumor biology rather than tumor burden, MAF may be a promising biomarker for the dynamic assessment of treatment response and resistance.

Hybrid capture-based genomic profiling of circulating tumor DNA from patients with metastatic breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12569-e12569
Author(s):  
Xiaoxiang Guan ◽  
Hong Zhu ◽  
Wenzhuan Xie ◽  
Jing Zhao ◽  
Guoqiang Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Internal Tissue ◽  
Genomic Alterations ◽  
Invasive Approach ◽  
Hybrid Capture ◽  
Female Patients ◽  
Tumor Dna

e12569 Background: Breast cancer is the most common malignancy among women worldwide. It is particularly important to provide precise therapies based on genomic alterations, especially for metastatic breast cancers (MBC), which exhibit a high tumor heterogeneity and dynamic changes during the course of disease progression. However, genomic sampling upon metastatic tissue biopsy frequently encountered difficulties due to its inherent invasive approach such as insufficient samples and clinical risks. Our study aims to assess the genomic alternation landscape of metastatic breast cancer detected by blood-based circulating tumor DNA (ctDNA) and evaluate the assay performance. Methods: We performed hybrid capture-based next-generation sequencing (NGS) of 150 genes on ctDNA from 203 female patients with MBC. The mean sequencing depth was more than 3000×. The results were compared with our internal tissue genomic database (297 female patients with MBC) tested by NGS and TCGA database (N=982) tested by whole exome sequencing. Genomic alterations including single nucleotide variation (SNV), insertions/deletions, copy number variations, gene rearrangement and fusions were assessed. Results: Genomic data from 203 female patients with metastatic breast cancer were analyzed via ctDNA [median age 53 years (range, 46–61 years)]. Evidence of ctDNA as estimated by the maximum somatic allele frequency (MSAF) was detected in 95.6% of the patients (median=7.1 alterations/patient), and 97.0% of the patients had at least one characterized altered gene. The most frequently mutated genes identified for SNV occurred in TP53 (47.8%), PIK3CA (36.0%), and ESR1 (16.3%) upon ctDNA analysis and TP53 (73.2%), PIK3CA (38.4%), and ESR1 (4.0%) from our internal tissue database. However, in TCGA cohort, where most patients were presented with early stage diseases, the most mutated gene in terms of SNV was PIK3CA (32.5%), followed by TP53 (30.7%) and TTN (16.0%). The status of ERBB2 amplifications had a high concordance among ctDNA (14.8%), tissue (14.9%), and TCGA database (13.5%). The MSAF level was significantly higher for the fusion-present cases (P=0.048) or amplification cases (p<0.0001) than non-fusion or non-amplification cases. Conclusions: Our study has suggested that ctDNA profiling is a feasible approach for the molecular analysis in metastatic breast cancer and may better capture the mutational landscape of MBC for further clinical implications.

The impact of HER2 phenotype of circulating tumor cells in metastatic breast cancer: a study in 107 patients

2014 ◽  
Vol 74 (S 01) ◽  
Author(s):  
M Wallwiener ◽  
AD Hartkopf ◽  
S Riethdorf ◽  
J Nees ◽  
FA Taran ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
The Impact
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