Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases.

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Abstract

BACKGROUND: Central nervous system (CNS) involvement contributes to significant morbidity and mortality in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) and represents a major challenge for clinicians. Liquid biopsy of cerebrospinal fluid (CSF)-derived circulating tumour DNA (ctDNA) harbours clinically relevant genomic alterations in patients with CNS metastases and could be effective in tracking tumour evolution. METHODS: In a HER2-positive mBC patient with brain metastases, we applied droplet digital PCR (ddPCR) and next-generation whole exome sequencing (WES) analysis to measure ctDNA dynamic changes in CSF and plasma collected during treatment. RESULTS: Baseline CSF-derived ctDNA analysis revealed TP53 and PIK3CA mutations as well as ERBB2 and cMYC amplification. Post-treatment ctDNA analysis showed decreased markers level in plasma, consistent with extra-CNS disease control, while increased in the CSF, confirming poor treatment benefit in the CNS. DISCUSSION: Analysis of ctDNA in the CSF of HER2-positive mBC is feasible and could represent a useful companion for clinical management of brain metastases.
Original languageEnglish
Pages (from-to)e000253
JournalESMO Open
Volume2
Publication statusPublished - 2017

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Cerebrospinal Fluid
Breast Neoplasms
Neoplasm Metastasis
DNA
Brain
Neoplasms
Central Nervous System
Exome
Central Nervous System Diseases
human ERBB2 protein
Therapeutics
Morbidity
Biopsy
Polymerase Chain Reaction
Mutation
Mortality

Keywords

  • HER2 positive, breast cancer, cerebrospinal fluid, heterogeneity, liquid biopsy

Cite this

@article{2676372dcf004611b80182095cfc525d,
title = "Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases.",
abstract = "BACKGROUND: Central nervous system (CNS) involvement contributes to significant morbidity and mortality in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) and represents a major challenge for clinicians. Liquid biopsy of cerebrospinal fluid (CSF)-derived circulating tumour DNA (ctDNA) harbours clinically relevant genomic alterations in patients with CNS metastases and could be effective in tracking tumour evolution. METHODS: In a HER2-positive mBC patient with brain metastases, we applied droplet digital PCR (ddPCR) and next-generation whole exome sequencing (WES) analysis to measure ctDNA dynamic changes in CSF and plasma collected during treatment. RESULTS: Baseline CSF-derived ctDNA analysis revealed TP53 and PIK3CA mutations as well as ERBB2 and cMYC amplification. Post-treatment ctDNA analysis showed decreased markers level in plasma, consistent with extra-CNS disease control, while increased in the CSF, confirming poor treatment benefit in the CNS. DISCUSSION: Analysis of ctDNA in the CSF of HER2-positive mBC is feasible and could represent a useful companion for clinical management of brain metastases.",
keywords = "HER2 positive, breast cancer, cerebrospinal fluid, heterogeneity, liquid biopsy",
author = "Giulia Siravegna and Elena Geuna and Benedetta Mussolin and Giovanni Crisafulli and Alice Bartolini and Danilo Galizia and Laura Casorzo and Ivana Sarotto and Maurizio Scaltriti and Anna Sapino and Alberto Bardelli and Filippo Montemurro",
year = "2017",
language = "English",
volume = "2",
pages = "e000253",
journal = "ESMO Open",
issn = "2059-7029",
publisher = "BMJ Publishing Group",

}

TY - JOUR

T1 - Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases.

AU - Siravegna, Giulia

AU - Geuna, Elena

AU - Mussolin, Benedetta

AU - Crisafulli, Giovanni

AU - Bartolini, Alice

AU - Galizia, Danilo

AU - Casorzo, Laura

AU - Sarotto, Ivana

AU - Scaltriti, Maurizio

AU - Sapino, Anna

AU - Bardelli, Alberto

AU - Montemurro, Filippo

PY - 2017

Y1 - 2017

N2 - BACKGROUND: Central nervous system (CNS) involvement contributes to significant morbidity and mortality in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) and represents a major challenge for clinicians. Liquid biopsy of cerebrospinal fluid (CSF)-derived circulating tumour DNA (ctDNA) harbours clinically relevant genomic alterations in patients with CNS metastases and could be effective in tracking tumour evolution. METHODS: In a HER2-positive mBC patient with brain metastases, we applied droplet digital PCR (ddPCR) and next-generation whole exome sequencing (WES) analysis to measure ctDNA dynamic changes in CSF and plasma collected during treatment. RESULTS: Baseline CSF-derived ctDNA analysis revealed TP53 and PIK3CA mutations as well as ERBB2 and cMYC amplification. Post-treatment ctDNA analysis showed decreased markers level in plasma, consistent with extra-CNS disease control, while increased in the CSF, confirming poor treatment benefit in the CNS. DISCUSSION: Analysis of ctDNA in the CSF of HER2-positive mBC is feasible and could represent a useful companion for clinical management of brain metastases.

AB - BACKGROUND: Central nervous system (CNS) involvement contributes to significant morbidity and mortality in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) and represents a major challenge for clinicians. Liquid biopsy of cerebrospinal fluid (CSF)-derived circulating tumour DNA (ctDNA) harbours clinically relevant genomic alterations in patients with CNS metastases and could be effective in tracking tumour evolution. METHODS: In a HER2-positive mBC patient with brain metastases, we applied droplet digital PCR (ddPCR) and next-generation whole exome sequencing (WES) analysis to measure ctDNA dynamic changes in CSF and plasma collected during treatment. RESULTS: Baseline CSF-derived ctDNA analysis revealed TP53 and PIK3CA mutations as well as ERBB2 and cMYC amplification. Post-treatment ctDNA analysis showed decreased markers level in plasma, consistent with extra-CNS disease control, while increased in the CSF, confirming poor treatment benefit in the CNS. DISCUSSION: Analysis of ctDNA in the CSF of HER2-positive mBC is feasible and could represent a useful companion for clinical management of brain metastases.

KW - HER2 positive, breast cancer, cerebrospinal fluid, heterogeneity, liquid biopsy

M3 - Article

VL - 2

SP - e000253

JO - ESMO Open

JF - ESMO Open

SN - 2059-7029

ER -