Landscape of circulating tumour DNA in metastatic breast cancer

被引：45

作者：

Davis, Andrew A. ^{[1
,2
]}

Jacob, Saya ^{[1
]}

Gerratana, Lorenzo ^{[1
,2
,3
]}

Shah, Ami N. ^{[1
,2
]}

Wehbe, Firas ^{[2
]}

Katam, Neelima ^{[2
]}

Zhang, Qiang ^{[1
,2
]}

Flaum, Lisa ^{[1
,2
]}

Siziopikou, Kalliopi P. ^{[1
,2
,4
]}

Platanias, Leonidas C. ^{[1
,2
]}

Gradishar, William J. ^{[1
,2
]}

Behdad, Amir ^{[1
,2
,4
]}

Cristofanilli, Massimo ^{[1
,2
]}

机构：

[1] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Hematol & Oncol, Chicago, IL 60611 USA

[2] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, 710N Fairbanks Court,Olson Pavil,Suite 8-250A, Chicago, IL 60611 USA

[3] Univ Udine, Dept Med, Udine, Italy

[4] Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA

来源：

EBIOMEDICINE | 2020年 / 58卷

基金：

美国国家卫生研究院;

关键词：

Circulating tumour DNA; cell-free DNA; Next-generation sequencing; Genomics; Metastatic breast cancer; CELL-FREE DNA; ESR1; MUTATIONS; HER2; EFFICACY;

D O I：

10.1016/j.ebiom.2020.102914

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: We describe the genomic landscape of circulating tumour DNA (ctDNA) across pathological sub-types of metastatic breast cancer. 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: 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: 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. (c) 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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