Liquid biopsy for HER2-positive breast cancer brain metastasis: the role of the cerebrospinal fluid

Mattos-Arruda, Leticia De

doi:10.1136/esmoopen-2017-000270

Cited by 16 publications

(12 citation statements)

References 19 publications

(14 reference statements)

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“…Therefore, in this study, we aimed to compare the results from CSF ctDNA with plasma ctDNA, plasma CTCs, and brain tissue specimens in patients with brain metastasis from NSCLC. The assessment of CSF ctDNA could provide a snapshot of what actually occurs in brain metastases, to more precisely guide therapy . Sequencing of CSF ctDNA revealed specific mutation patterns in driver genes among patients with NSCLC and brain metastases.…”

Section: Discussionmentioning

confidence: 99%

“…The assessment of CSF ctDNA could provide a snapshot of what actually occurs in brain metastases, 11,15 to more precisely guide therapy. [16][17][18] Sequencing of CSF ctDNA revealed specific mutation patterns in driver genes among patients with NSCLC and brain metastases. This is the first study comparing CSF ctDNA, blood ctDNA, CTCs, and brain tissue in patients with NSCLC and brain metastases.…”

Section: Discussionmentioning

confidence: 99%

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Detection of circulating tumor DNA from non‐small cell lung cancer brain metastasis in cerebrospinal fluid samples

Yang

Xing

et al. 2020

Thoracic Cancer

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Background Evaluating the molecular characteristics of brain metastases is limited by difficult access and by the blood–brain barrier, which prevents circulating tumor DNA (ctDNA) from entering the blood. In this study, we aimed to compare the sequencing results from cerebrospinal fluid (CSF) ctDNA versus plasma ctDNA, plasma circulating tumor cells (CTCs), and brain tissue specimens from patients with brain metastasis from non‐small cell lung cancer (NSCLC). Methods This was a prospective study of 21 consecutive patients with NSCLC and brain metastasis diagnosed between April 2018 and January 2019. Samples of CSF and peripheral blood were obtained from all 21 patients. Brain tissues were obtained from five patients after surgical resection. Next‐generation sequencing was performed using the Ion system. Single nucleotide variants (SNVs) and small insertions or deletions (indels) were searched. Results Mutations were detected in the CSF ctDNA of 20 (95.2%) patients. The detection rate of epidermal growth factor receptor (EGFR) mutations in CSF ctDNA was 57.1% (12/21) whereas this rate was only 23.8% (5/21) in peripheral blood ctDNA and in CTCs. EGFR mutations were found in the CSF of 9 of 11 (81.8%) patients with leptomeningeal metastases, as compared with three of 10 (30%) patients with brain parenchymal metastases. Mutations were also detected in KIT, PIK3CA, TP53, SMAD4, ATM, SMARCB1, PTEN, FLT3, GNAS, STK11, MET, CTNNB1, APC, FBXW7, ERBB4, and KDR (all >10%). The status of EGFR and TP53 mutations was consistent between CSF ctDNA and brain lesion tissue in all five patients. Conclusion Sequencing of CSF ctDNA revealed specific mutation patterns in driver genes among patients with NSCLC and brain metastasis. Key points In some small‐sample studies, the importance of cerebrospinal fluid in guiding the treatment of cancerous brain lesions has been verified in that it may reflect genomic mutations of brain tumors relatively accurately. Cerebrospinal fluid is a new form of liquid biopsy that can be helpful in improving the management of patients with brain metastasis from non‐small cell lung cancer by detecting genetic abnormalities specific to brain metastases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Detection of circulating tumor DNA from non‐small cell lung cancer brain metastasis in cerebrospinal fluid samples

Yang

Xing

et al. 2020

Thoracic Cancer

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“…EGJC is the least studied cancer for HER2 gene status. Moreover, De Mattos-Arruda indicated that ctDNA from CSF (cerebro-spinal uid) had the potential to identify brain metastasis-speci c actionable genomic alterations that may facilitate the design of personalised treatments in breast cancer patients [26]. There are indication that HER2 gene copy number can be assessed in serum of peripheral blood as a predictive marker for quali cation or monitoring of targeted treatment with trastuzumab in breast cancer patients.…”

Section: Discussionmentioning

confidence: 99%

HER2 gene assessment in liquid biopsy of gastric and esophagogastric junction cancer patients qualified for surgery

Grenda

Wojas‐Krawczyk

Skoczylas

et al. 2020

Preprint

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Background Amplification of HER2 gene (ERBB2) and overexpression of HER2 protein on cancer cells are found in 10-26% of gastric cancer (GC) and esophagogastric junction cancer (EGJC). Gene copy number variation (CNV) could be detected in these patients in liquid biopsy and in cancer cells.Methods We analysed HER2 gene CNV used qPCR method in 87 sera collected from GC and EGJC patients before surgical treatment and in 40 sera obtained from healthy donors. HER2 gene CNV was also assessed in formalin-fixed paraffin-embedded (FFPE) tumor tissue. Furthermore, we assessed the number of HER2 gene copies and HER2 expression in cancer cells using the fluorescent in situ hybridization method (FISH) and immunohistochemistry (IHC).Results We found that the HER2 gene copy number in liquid biopsy was higher in GC and EGJC patients compared to healthy people (p=0.01). Moreover, EGJC patients had higher number of HER2 gene copies than healthy donors (p=0.0016). HER2 CNV examination could distinguish healthy individuals and patients with gastric or esophagogastric junction cancers with sensitivity and specificity of 58% and 98% (AUC=0.707, 95% CI: 0.593-0.821, p=0.004). We found that patients with a high copy number of the HER2 gene in the tumor tissue assessed by qPCR (but not by FISH) have significantly more often a high number of HER2 gene copies in liquid biopsy (p=0.04).Conclusions We suggested that HER2 testing in liquid biopsy could be used as an auxiliary method to analysis of HER2 status in tumor tissue in gastric or esophagogastric junction cancers.

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“…Liquid biopsies can detect the HER-2 released into the peripheral blood from tumor tissues, even in patients with multiple tumor foci. Liquid biopsies also allow the detection of cancer-associated alleles in the blood and provide a genetic landscape for primary and metastatic tumors ( 16 , 37 ). A liquid biopsy detects all circulating HER-2 mRNA released by breast tumors, and can be used for quantification by RT-qPCR ( 31 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

“…Only tumors with scores of 2+ or 3+ with a FISH ratio ≥2.0 are defined as HER-2-positive ( 15 ). In addition to determining HER-2 status in tissue specimens, there has been a high level of interest in liquid biopsy to determine the level of circulating HER-2, due to its accessibility and the possibility for the serial monitoring of the tumor response to therapy ( 16 ). The detection of HER-2 mRNA-positive circulating tumor cells (CTCs) in peripheral blood is considered a useful tool in the early diagnosis of breast cancer, and an independent prognostic factor for disease-free survival (DFS) ( 17 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

Circulating HER‑2 mRNA in the peripheral blood as a potential diagnostic and prognostic biomarker in females with breast cancer

Meng²,

Yang

et al. 2018

Oncol Lett

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Breast cancer is a prevalent malignant cancer worldwide, and a lack of defined biomarkers for early prognostication contributes to its high associated mortality rate, especially in human epidermal growth factor receptor 2 (HER-2)-positive breast cancer. In the present study, HER-2 mRNA levels in patients were detected prior to surgery and during neoadjuvant chemotherapy to explore its potential diagnostic and prognostic value. Blood samples were collected from 70 patients with breast cancer, including 50 HER-2-negative and 20 HER-2-positive patients, prior to and following surgery (postoperative, n=13; neoadjuvant chemotherapy, n=5); the control group included 35 samples from healthy individuals. The relative mRNA level of HER-2 in blood was determined by one-step reverse transcription-quantitative polymerase chain reaction. HER-2 expression curves of measurements taken during neoadjuvant chemotherapy were compared with the tumor size. A significant difference in the blood HER-2 mRNA level was observed between healthy women and patients with breast cancer (P<0.0001). A cutoff value of 1.512 was established for the circulating HER-2 level in healthy subjects based on the upper 95% confidence interval value of samples from the control group. The level of HER-2 mRNA in blood was associated with the HER-2 status, Ki-67 expression, and lymphovascular invasion in primary tumor tissue samples; however, there was no association with the lymph node status, tumor stage, tumor grade, tumor size, patient age, estrogen or progesterone receptor status of the primary tumor. HER-2 mRNA levels were associated with the response rate, as determined by primary tumor size, in patients who received neoadjuvant chemotherapy. In conclusion, baseline and early changes in peripheral blood HER-2 mRNA indicated that HER-2 mRNA may be a potential diagnostic biomarker for breast cancer and a prognostic marker for predicting the efficacy of neoadjuvant therapy.

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Liquid biopsy for HER2-positive breast cancer brain metastasis: the role of the cerebrospinal fluid

Cited by 16 publications

References 19 publications

Detection of circulating tumor DNA from non‐small cell lung cancer brain metastasis in cerebrospinal fluid samples

Detection of circulating tumor DNA from non‐small cell lung cancer brain metastasis in cerebrospinal fluid samples

HER2 gene assessment in liquid biopsy of gastric and esophagogastric junction cancer patients qualified for surgery

Circulating HER‑2 mRNA in the peripheral blood as a potential diagnostic and prognostic biomarker in females with breast cancer

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