Siravegna Giulia, Geuna Elena, Mussolin Benedetta, Crisafulli Giovanni, Bartolini Alice, Galizia Danilo, Casorzo Laura, Sarotto Ivana, Scaltriti Maurizio, Sapino Anna, Bardelli Alberto, Montemurro Filippo
Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
Investigative Clinical Oncology (INCO), Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
ESMO Open. 2017 Oct 9;2(4):e000253. doi: 10.1136/esmoopen-2017-000253. eCollection 2017.
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.
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.
Baseline CSF-derived ctDNA analysis revealed and mutations as well as and c 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.
Analysis of ctDNA in the CSF of HER2-positive mBC is feasible and could represent a useful companion for clinical management of brain metastases.
中枢神经系统（CNS）受累导致人表皮生长因子受体2（HER2）阳性转移性乳腺癌（mBC）患者出现显著的发病率和死亡率，这对临床医生来说是一项重大挑战。脑脊液（CSF）来源的循环肿瘤DNA（ctDNA）的液体活检在CNS转移患者中存在临床相关的基因组改变，并且可能有效地追踪肿瘤进展。
在一名患有脑转移的HER2阳性mBC患者中，我们应用液滴数字PCR（ddPCR）和下一代全外显子测序（WES）分析来测量治疗期间收集的CSF和血浆中ctDNA的动态变化。
基线CSF来源的ctDNA分析显示 和 突变以及 和c扩增。治疗后ctDNA分析显示血浆中标志物水平降低，与CNS外疾病控制一致，而CSF中升高，证实CNS治疗获益不佳。
HER2阳性mBC患者CSF中ctDNA的分析是可行的，并且可能是脑转移临床管理的有用辅助手段。
