Landscape of circulating tumour DNA in metastatic breast cancer.
Adult
Aged
Breast Neoplasms
/ blood
Circulating Tumor DNA
/ genetics
DNA Copy Number Variations
Female
Gene Frequency
Gene Regulatory Networks
Genetic Heterogeneity
High-Throughput Nucleotide Sequencing
Humans
Middle Aged
Neoplasm Metastasis
Polymorphism, Single Nucleotide
Sequence Analysis, DNA
/ methods
Circulating tumour DNA
Genomics
Metastatic breast cancer
Next-generation sequencing
cell-free DNA
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
29
04
2020
revised:
30
06
2020
accepted:
10
07
2020
pubmed:
25
7
2020
medline:
8
6
2021
entrez:
25
7
2020
Statut:
ppublish
Résumé
We describe the genomic landscape of circulating tumour DNA (ctDNA) across pathological subtypes of metastatic breast cancer. 255 clinically annotated patients with ctDNA testing by Guardant360 were stratified into HR+, HER2+, and TNBC cohorts. Frequency and heterogeneity of alterations were reported. Paired ctDNA and tissue sequencing were compared for a subset of patients. The association of ctDNA and metastatic sites of disease on imaging was also assessed. 89% of patients had at least one ctDNA alteration detected. The most common single nucleotide variants (SNVs) for HR+ patients were PIK3CA, ESR1, and TP53. For HER2+, these were TP53, PIK3CA, and ERBB2 with ERBB2 as the most frequent copy number variant (CNV). For TNBC, the most common SNVs were TP53 and PIK3CA, and the most frequent CNVs were MYC, CCNE1, and PIK3CA. TNBC patients had a significantly higher mutant allele frequency (MAF) of the highest variant compared to HR+ or HER2+ patients (P<0.05). Overall, alterations in PIK3CA, ESR1, and ERBB2 were observed in 39.6%, 16.5%, and 21.6% of patients, respectively. Agreement between blood and tissue was 79-91%. MAF and number of alterations were significantly associated with number of metastatic sites on imaging (P<0.0001). These data demonstrate the genetic heterogeneity of metastatic breast cancer in blood, the high prevalence of clinically actionable alterations, and the potential to utilise ctDNA as a surrogate for tumour burden on imaging. Lynn Sage Cancer Research Foundation, OncoSET Precision Medicine Program, and REDCap support was funded by the National Institutes of Health UL1TR001422.
Sections du résumé
BACKGROUND
BACKGROUND
We describe the genomic landscape of circulating tumour DNA (ctDNA) across pathological subtypes of metastatic breast cancer.
METHODS
METHODS
255 clinically annotated patients with ctDNA testing by Guardant360 were stratified into HR+, HER2+, and TNBC cohorts. Frequency and heterogeneity of alterations were reported. Paired ctDNA and tissue sequencing were compared for a subset of patients. The association of ctDNA and metastatic sites of disease on imaging was also assessed.
FINDINGS
RESULTS
89% of patients had at least one ctDNA alteration detected. The most common single nucleotide variants (SNVs) for HR+ patients were PIK3CA, ESR1, and TP53. For HER2+, these were TP53, PIK3CA, and ERBB2 with ERBB2 as the most frequent copy number variant (CNV). For TNBC, the most common SNVs were TP53 and PIK3CA, and the most frequent CNVs were MYC, CCNE1, and PIK3CA. TNBC patients had a significantly higher mutant allele frequency (MAF) of the highest variant compared to HR+ or HER2+ patients (P<0.05). Overall, alterations in PIK3CA, ESR1, and ERBB2 were observed in 39.6%, 16.5%, and 21.6% of patients, respectively. Agreement between blood and tissue was 79-91%. MAF and number of alterations were significantly associated with number of metastatic sites on imaging (P<0.0001).
INTERPRETATION
CONCLUSIONS
These data demonstrate the genetic heterogeneity of metastatic breast cancer in blood, the high prevalence of clinically actionable alterations, and the potential to utilise ctDNA as a surrogate for tumour burden on imaging.
FUNDING
BACKGROUND
Lynn Sage Cancer Research Foundation, OncoSET Precision Medicine Program, and REDCap support was funded by the National Institutes of Health UL1TR001422.
Identifiants
pubmed: 32707446
pii: S2352-3964(20)30289-9
doi: 10.1016/j.ebiom.2020.102914
pmc: PMC7381501
pii:
doi:
Substances chimiques
Circulating Tumor DNA
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102914Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest Andrew A. Davis reports receiving travel support from Menarini Silicon Biosystems, outside the submitted work; Lorenzo Gerratana reports non-financial support from Menarini Silicon Biosystems, personal fees from Lilly, outside the submitted work; Ami N. Shah reports personal fees from Abbvie, personal fees from Taiho, personal fees from Daiichi-Sankyo, outside the submitted work; Amir Behdad reports personal fees from Pfizer, personal fees from Foundation Medicine, personal fees from Bayer, outside the submitted work. Massimo Cristofanilli reports personal fees from Foundation Medicine, personal fees from Lilly, grants and personal fees from Pfizer, personal fees from Cytodyn, personal fees from Sermonix, grants and personal fees from G1Therapeutics, outside the submitted work.
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