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 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.

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.

Comparison of HER2 status between primary tumor and disseminated tumor cells in␣primary breast cancer patients

2006 ◽  
Vol 98 (2) ◽  
pp. 179-184 ◽  
Author(s):  
Erich F. Solomayer ◽  
Sven Becker ◽  
Graziella Pergola-Becker ◽  
Robert Bachmann ◽  
Bernhard Krämer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Primary Tumor ◽  
Primary Breast Cancer ◽  
Disseminated Tumor Cells ◽  
Her2 Status ◽  
Breast Cancer Patients

Serial monitoring for circulating cancer cells in blood samples of stage 1–4 breast cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 623-623
Author(s):  
K. H. Tkaczuk ◽  
N. S. Tait ◽  
K. Chua ◽  
F. Feldman ◽  
S. A. Lesko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Primary Tumor ◽  
Receptor Expression ◽  
Breast Cancer Patients ◽  
Blood Samples ◽  
Circulating Cancer Cells ◽  
Her 2 ◽  
Stage 1

623 Serial monitoring for presence, number & characterization of circulating cancer cells (CCC) may provide valuable information that may be relevant to prognosis and treatment outcomes of breast cancer patients (BCP). We conducted a serial blood sampling study at the University of Maryland in BCP with stage 1–4 breast carcinoma. 15–20 ml of venous blood were collected before the start of systemic therapy and periodically thereafter & processed using negative selection method with double-gradient centrifugation & magnetic cell sorting to remove WBCs. Digital images of FITC-positive epithelial cells were acquired with a fluorescence microscope & counted. CCC from 41 patients (Pts) were also stained with Trastuzu-mAb-532 to quantify the HER-2/neu cell surface receptor expression relative to a fluorescence standard. 105 Pts were accrued & 415 blood samples tested (median number of samples/pt; 4 (1–8). During the 24 mos. monitoring period CCC were detected in 57 of 105 pts (54%). The Table below shows that presence of >10 CCC/sample is associated with decreased survival and increased probability of having metastatic disease.(Exact chi-square test for presence vs. absence of metastatses in A, B, C, D groups, P < 0.0001; Fisher’s exact test to compare individual groups: for B vs C+ D, P < 0.001; B vs C, P=0.001). HER-2/neu expression was assessed in CCC of 25 pts (minimum of 4 CCC per sample) as compared with strongly HER-2/neu positive control cell line SKBR-3. 10 Pts were positive & 15 negative for HER-2/neu over-expression in CCC. CCC data & primary tumor data concurred in 6 of 7 Her-2/neu primary tumor tissue positive Pts & in 12 of 13 Her-2/neu primary tissue negative Pts. For 5 Pts tissue data was not available. Conclusions: Increasing CCC numbers/sample appear to correlate with adverse outcome of BCP. Our CCC Test may provide valuable information about prognosis of stage 1–4 BCP. HER-2/neu expression could be quantified in individual CCC & concurred with primary tumor data in 90% of Pts. Supported by NCI Grant CA081903 [Table: see text] [Table: see text]

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]

Estrogen receptor (ER) status of disseminated tumor cells in the bone marrow of breast cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21013-21013
Author(s):  
F. N. Tanja ◽  
N. Krawczyk ◽  
D. Wallwiener ◽  
S. Becker ◽  
E. Solomayer
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Primary Tumor ◽  
Hormone Receptor ◽  
Primary Breast Cancer ◽  
Disseminated Tumor Cells ◽  
Breast Cancer Patients ◽  
Primary Tumors

21013 Background: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of primary breast cancer patients is associated with poor prognosis. These patients may benefit from adjuvant endocrine therapy since cytotoxic agents are not able to completely eliminate DTCs as previously shown. Only patients with hormone receptor positive breast cancer are eligible for hormonal treatment. The ERa status is routinely defined in primary tumor tissue. However, the ERa status of DTC may differ compared to the primary tumor. Therefore, the aims of this study were (1) to determine the ERa status of DTC in BM of breast cancer patients, (2) and to compare the ERa status of DTC and corresponding primary tumors. Methods: BM aspirates from 251 primary breast cancer patients were included into the study. A double immunofluorescence staining procedure was established for the identification of cytokeratin-positive (CK)/ERa positive cells. ERa status of the primary tumor was immunohistochemically assessed using the same antibody against ERa. Results: In 105 of 251 (42%) breast cancer patients CK-positive cells could be detected in BM. The number of detected cells ranged between 1 and 13 / cells per 2*106 mononuclear cells. Disseminated tumor cells demonstrated ERa positivity in 13 (12%) of these 105 patients. The ERa expression on DTC was heterogeneous in 10 of 13 (79%) patients. Concordance rate of ERa status between primary tumor and DTC was 27%. Only 11 of 83 patients with ER a positive tumors had also ERa positives DTC. Conclusions: (1)The hormone receptor status between primary tumor and corresponding DTC is disconcordant. (2)This discrepancy may explain the rate of non-responders to adjuvant endocrine therapy despite ER-positive primary tumors. (3)These patients may benefit from adjuvant therapy regimens based on antibody strategies or bisphosphonates. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document