scholarly journals Whole Genome Sequencing in single CTC improves clinical outcome in Her-2 negative breast cancer patients

2020 ◽  
Author(s):  
Yongping Li ◽  
Hao Yuan ◽  
Bin Zhang ◽  
Xiaofei Jiang ◽  
Minghua Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liver Metastases ◽  
Whole Genome Sequencing ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Genome Sequencing ◽  
Tumor Tissue ◽  
Whole Genome ◽  
Breast Cancer Patients ◽  
Her 2

Abstract Backgroud: Tumor tissues are usually highly heterogeneous and difficult to characterize which could mislead treatment strategy. Circulating tumor cells (CTCs) represent the most active and invasive tumor cells. This study retrospectively investigated the feasibility of individualized treatment of breast cancer patients based on genome sequencing of single cell CTC. Twenty-four CTCs were identified in three patients with breast cancer. For each patient, one polyploid CTC was captured and on which the whole genome sequencing (WGS) was performed. Based on the histopathological Her-2 status in tumor tissue and the HER2 gene status in WGS results of CTC, we adjusted treatment strategies, and monitored disease progression. Results: Patient ID1 and ID2 are with Her-2 protein overexpression in primary tumors and HER2 gene amplification in the DNA of CTCs. In patient ID3, histological examination of primary tumor and liver metastases revealed Her-2 negative, but the WGS analysis of CTC showed that the HER2 gene was amplified. After adjusting treatment by adding Her-2 inhibitors according to the results of CTC sequencing, the liver metastases and pleural effusion were significantly reduced 2 month later, CTC number and ctDNA burden were decreased, and 18-month progression-free survival (PFS) was recorded. In addition, some potential therapeutic targets and mutations in drug-resistant genes were found. Conclusions: The results of CTC sequencing effectively guided treatment of a patient with HER2 gene amplification in CTC but with Her-2 negative on tumor tissue. CTC sequencing is useful in resolving the heterogeneity of tumors and providing precision medicine for patients.

scholarly journals Whole Genome Sequencing in single CTC improves clinical outcome in Her-2 negative breast cancer patients

2020 ◽  
Author(s):  
Bo Yu ◽  
Yongping Li ◽  
Hao Yuan ◽  
Bin Zhang ◽  
Xiaofei Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Genome Sequencing ◽  
Primary Tumor ◽  
Tumor Tissue ◽  
Whole Genome ◽  
Breast Cancer Patients ◽  
Her2 Gene ◽  
Her 2

Abstract Background Tumor tissues are usually highly heterogeneous and difficult to characterize which could mislead treatment strategy. Circulating tumor cells (CTCs) represent the most active and invasive tumor cells. This study explored the feasibility of individualized treatment of breast cancer patients based on genome sequencing of single cell CTC. Methods Twenty-four CTCs were identified in three patients with breast cancer. For each patient, one polyploid CTC was captured and on which the whole genome sequencing (WGS) was performed. Based on the histopathological Her-2 status in tumor tissue and the HER2 gene status in WGS results of CTC, we adjusted treatment strategies, and monitored disease progression. Results Patient ID1 and ID2 are Her-2 positive in both primary tumor and HER2 abnormal in the DNA of CTC. In patient ID3, histological examination of primary tumor and liver metastases revealed Her-2 negative, but the WGS analysis of CTC showed that the HER2 gene was amplified and mutated. After adjusting treatment according to the results of CTC sequencing, the liver metastases and pleural effusion were significantly reduced, CTC number and ctDNA burden were decreased. In addition, some potential therapeutic targets and mutations in drug-resistant genes were found. Conclusion The results of CTC sequencing effectively guided treatment of a patient with HER2 gene amplification/mutation in CTC but with Her-2 negative on tumor tissue. CTC sequencing is useful in resolving the heterogeneity of tumors and providing precision medicine for patients.

scholarly journals High chromosome instability identified by low-pass whole-genome sequencing assay is associated with TP53 copy loss and worse prognosis in BRCA1 germline mutation breast cancer

Breast Cancer ◽  
2021 ◽  
Author(s):  
Liang Zhu ◽  
Jia-Ni Pan ◽  
Ziliang Qian ◽  
Wei-Wu Ye ◽  
Xiao-Jia Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Whole Genome Sequencing ◽  
Cancer Patients ◽  
Genome Sequencing ◽  
Germline Mutation ◽  
Chromosome Instability ◽  
Whole Genome ◽  
Breast Cancer Patients ◽  
Two Samples ◽  
Low Pass

Abstract Background Though BRCA1 mutation is the most susceptible factor of breast cancer, its prognostic value is disputable. Here in this study, we use a novel method which based on whole-genome analysis to evaluate the chromosome instability (CIN) value and identified the potential relationship between CIN and prognosis of breast cancer patients with germline-BRCA1 mutation. Materials and methods Sanger sequencing or a 98-gene panel sequencing assay was used to screen for BRCA1 germline small mutations in 1151 breast cancer patients with high-risk factors. MLPA assay was employed to screen BRCA1 large genomic rearrangements in familial breast cancer patients with BRCA1 negative for small mutations. Thirty-two samples with unique BRCA1 germline mutation patterns were further subjected to CIN evaluation by LPWGS (low-pass whole-genome sequencing) technology. Results Firstly, 113 patients with germline BRCA1 mutations were screened from the cohort. Further CIN analysis by the LPWGS assay indicated that CIN was independent from the mutation location or type of BRCA1. Patients with high CIN status had shorter disease-free survival rates (DFS) (HR = 6.54, 95% CI 1.30–32.98, P = 0.034). The TP53 copy loss was also characterized by LPWGS assay. The rates of TP53 copy loss in CIN high and CIN low groups were 85.71% (12/14) and 16.67% (3/18), respectively. Conclusion CIN-high is a prognostic factor correlated with shorter DFS and was independent with the germline BRCA1 mutation pattern. Higher CIN values were significantly correlated with TP53 copy loss in breast cancer patients with germline BRCA1 mutation. Our results revealed a reliable molecular parameter for distinguishing patients with poor prognosis from the BRCA1-mutated breast cancer patients.

Circulating Tumor Cells in HER-2 Positive Metastatic Breast Cancer Patients Treated with Trastuzumab and Chemotherapy

2009 ◽  
Vol 24 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Raquel A. Nunes ◽  
Xiaochun Li ◽  
Soonmo Peter Kang ◽  
Harold Burstein ◽  
Lisa Roberts ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Response ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Her 2

The detection of circulating tumor cells (CTCs) in peripheral blood may have important prognostic and predictive implications in breast cancer treatment. A limitation in this field has been the lack of a validated method of accurately measuring CTCs. While sensitivity has improved using RT-PCR, specificity remains a major challenge. The goal of this paper is to present a sensitive and specific methodology of detecting CTCs in women with HER-2-positive metastatic breast cancer, and to examine its role as a marker that tracks disease response during treatment with trastuzumab-containing regimens. The study included patients with HER-2-positive metastatic breast cancer enrolled on two different clinical protocols using a trastuzumab-containing regimen. Serial CTCs were measured at planned time points and clinical correlations were made. Immunomagnetic selection of circulating epithelial cells was used to address the specificity of tumor cell detection using cytokeratin 19 (CK19). In addition, the extracellular domain of the HER-2 protein (HER-2/ECD) was measured to determine if CTCs detected by CK19 accurately reflect tumor burden. The presence of CTCs at first restaging was associated with disease progression. We observed an association between CK19 and HER-2/ECD. The association of HER-2/ECD with clinical response followed a similar pattern to that seen with CK19. Finally, the absence of HER-2/ECD at best overall response and a change of HER-2/ECD from positive at baseline to negative at best overall response was associated with favorable treatment response. Our study supports the prognostic and predictive role of the detection of CTCs in treatment of HER-2-positive metastatic breast cancer patients. The association between CK19 and markers of disease burden is in line with the concept that CTCs may be a reliable measure of tumor cells in the peripheral blood of patients with metastatic breast cancer. The association of CTCs at first restaging with treatment failure indicates that CTCs may have a role as surrogate markers to monitor treatment response.

Prospective monitoring of circulating tumor cells in breast cancer patients treated with primary systemic therapy—A translational project of the German Breast Group study GeparQuattro

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21085-21085 ◽  
Author(s):  
V. Mueller ◽  
S. Riethdorf ◽  
S. Loibl ◽  
M. Komor ◽  
J. Houber ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
Primary Diagnosis ◽  
Breast Cancer Patients ◽  
Primary Systemic Therapy ◽  
Her 2 ◽  
The Impact

21085 Background: The impact of circulating tumor cells (CTC) in patients with primary breast cancer is still unclear. Primary systemic treatment (PST) allows the assessment of therapeutic efficacy in breast cancer patients without long follow-up periods. Here we present first results on the presence of CTC in peripheral blood of patients enrolled in the “GeparQuattro” study. Methods: This study incorporates three different chemotherapy approaches and additional Trastuzumab (Herceptin®) treatment for patients with HER-2/neu-positive tumors. Recruitment finished in November 2006 and not all patients have completed therapy yet. We used the CellSearch™ system to evaluate CTC before PST from 245 patients and after PST from 67 patients. CTC from 45 samples were also examined for HER-2/neu expression by immunocytochemistry in the CellSearch™ system. Results: Before PST we detected CTC in 54/245 patients (22%). CTC numbers in 7.5 mL blood ranged between 1 and 200 (mean 6.5). In 8 CTC-positive samples (3.3%) = 5 CTC were found. Her-2/neu-positive CTC were observed in 25/45 cases (55.6%). CTC could be detected in 7/67 patients (10.4%) after PST (1 or 2 CTC). Before and after PST blood was analyzed from 43 patients, 27 of them were CTC-negative at both time points. Ten initially CTC-positive cases were CTC-negative after PST whereas 6 cases were detected CTC-positive after PST although no CTC could be found before PST. Conclusions: With the CellSearch™ system CTC can be detected in non-metastatic breast cancer patients at primary diagnosis and also after PST. To our knowledge, this is the largest study evaluating the presence of CTC in this context. With the availability of response information from more patients, it will be possible to examine the correlation between the incidence of CTC and response as well as kinetics of HER-2/neu expression during Trastuzumab treatment. [Table: see text]

Molecular profiling of circulating tumor cells in the peripheral blood of patients with primary and metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20033-20033
Author(s):  
N. Fersis ◽  
V. Deckwart ◽  
A. Leitz ◽  
M. Weber ◽  
J. Rom ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Breast Carcinoma ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Rt Pcr ◽  
Her 2

20033 Background: The purpose of this study was detection and expression profiling of circulating tumor cells (CTC) in breast cancer patients. Methods: Two separate probes of 5 mL peripheral EDTA-blood from patients with primary breast cancer (n=167) and metastatic disease (n=111) were used for immunomagnetic tumor cell selection. Targets for preanalytical enrichment were the antigens EpCAM and MUC-1. Separated cells were lysed and used for mRNA isolation and c-DNA synthesis. The breast carcinoma-associated transcripts EpCAM, MUC-1, HER-2, claudin7, cytokeratin 19, mammaglobin 1, prostate-specific ets factor (PSE) and survivin were amplified by three separate multiplex RT-PCR reactions. Amplicons were analysed by capillary electrophoresis with the Agilent Bioanalyzer 2100. Specificity of the RT-PCR was confirmed by examination of blood of healthy donors. Results: Sensitivity for every single transcript was adjusted to 2 tumor cells per 5 ml blood. Tumor-associated transcripts were detected in 31 of of 167 (18.5%) patients with primary breast cancer and in 46 of 111 (41%) patients with metastatic disease. The marker with the highest incidence in both groups was MUC-1, with a positivity rate of 81%. Tumor-associated transcripts were heterogenouosly expressed, however multiple markers were identified in more than 50% of the positive samples. Conclusion: Using a combination of preanalytical immunomagnetic tumor cell enrichment followed by a multigen RT-PCR approach we describe a sensitive detection system for breast carcinoma cells. In this study a panel of 8 genes overexpressed at high levels in metastatic breast cancer was selected for the identification of disseminated tumor cells in the peripheral blood of breast cancer patients. HER-2, survivin as a unique member of the inhibitor of apotosis protein family, as well as PSE identified in circulating breast cancer cells may serve as prognostic indicators of tumor progression and could represent valid targets for new individualized therapeutic interventions. No significant financial relationships to disclose.

Circulating tumor cells in HER-2 positive metastatic breast cancer patients treated with trastuzumab and chemotherapy

2009 ◽  
Vol 24 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Raquel A. Nunes ◽  
Xiaochun Li ◽  
Soonmo Peter Kang ◽  
Harold Burstein ◽  
Lisa Roberts ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Her 2

scholarly journals Whole-genome analysis of single disseminated tumor cells isolated from bone marrow of breast cancer patients

10.1038/87284 ◽  
2001 ◽  
Vol 27 (S4) ◽  
pp. 85-85
Author(s):  
Oleg Schmidt-Kittler ◽  
Angela Daskalakis ◽  
Andre Ahr ◽  
Julie Waldispuhl ◽  
Christoph Klein
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Genome Analysis ◽  
Disseminated Tumor Cells ◽  
Whole Genome ◽  
Breast Cancer Patients ◽  
Whole Genome Analysis

scholarly journals Comparison of Circulating Tumour DNA and Extracellular Vesicle DNA by Low-Pass Whole-Genome Sequencing Reveals Molecular Drivers of Disease in a Breast Cancer Patient

Biomedicines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 14
Author(s):  
Olivia Ruhen ◽  
Bob Mirzai ◽  
Michael E. Clark ◽  
Bella Nguyen ◽  
Carlos Salomon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number Variants ◽  
Extracellular Vesicle ◽  
Whole Genome ◽  
Breast Cancer Patients ◽  
Low Pass ◽  
Serial Samples ◽  
Circulating Tumour Dna

There is increasing recognition of circulating tumour DNA (ctDNA) as a non-invasive alternative to tumour tissue for the molecular characterisation and monitoring of disease. Recent evidence suggests that cancer-associated changes can also be detected in the DNA contained within extracellular vesicles (EVs). As yet, there has been limited investigation into the relationship between EV DNA and ctDNA, and no studies have examined the EV DNA of breast cancer patients. The aim of this study was to use low-pass whole-genome sequencing to identify copy number variants (CNVs) in serial samples of both ctDNA and EV DNA from a patient with breast cancer. Of the 52 CNVs identified in tumour DNA, 36 (69%) were detected in at least one ctDNA sample and 13 (25%) in at least one EV DNA sample. The number of detectable variants in ctDNA and EV DNA increased over the natural history of the patient’s disease, which was associated with progression to cerebral metastases. This case study demonstrates that, while CNVs are detectable in patient EV DNA, ctDNA has greater sensitivity than EV DNA for serial monitoring of breast cancer.

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