Prognostic Significance of Disseminated Tumor Cells as Detected by Quantitative Real-Time Reverse-Transcriptase Polymerase Chain Reaction in Patients with Breast Cancer

Benoy, Ina; Elst, Hilde; Philips, M. E.; Wuyts, Hilde; Dam, Peter van; Scharpé, Simon; Marck, Eric Van; Vermeulen, Peter; Dirix, Luc

doi:10.3816/cbc.2006.n.024

Cited by 29 publications

(26 citation statements)

References 20 publications

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“…In addition, in these studies, biomarkers expression was most frequently evaluated on a single metastatic site, assuming that this site would be representative of the bulk of metastatic disease. The use of modern technologies allowing for the isolation of CTCs from the peripheral blood of cancer patients has enabled the undertaking of studies aiming to biologically characterize metastatic tumors [25][26][27][28][29][30][31][32][33]. Theoretically, CTCs isolation and biocharacterization may become a real time and minimally invasive biopsy of the metastatic tumor and could provide the clinician with relevant information in terms of prognosis and prediction of treatment activity.…”

Section: Discussionmentioning

confidence: 99%

Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients

Pestrin

Bessi

Galardi

et al. 2009

Breast Cancer Res Treat

195

131

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Biocharacterization of circulating tumor cells (CTCs) in the peripheral blood of advanced breast cancer (ABC) patients may represent a real-time tumor biopsy. We assessed HER2 status on CTCs from blood samples of ABC patients. CTCs were separated and stained using the CellSearch System Ò . HER2 status was assessed by immunofluorescence and, when technically feasible, by fluorescence in situ hybridization. Blood samples were obtained from 66 ABC patients. Forty patients had a positive CTC sample (61%) and of these, 15 (37%) had HER2 ? CTCs. We found non-concordant results in 32% of cases: 29% (8/ 28) of HER2-negative primary tumors had HER2-positive CTCs and 42% (5/12) of HER2-positive primary tumors had HER2-negative CTCs (k = 0.278). Our study suggests that a subset of patients with HER2-negative primary tumors develops HER2-positive CTCs during disease progression.

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Section: Discussionmentioning

confidence: 99%

Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients

Pestrin

Bessi

Galardi

et al. 2009

Breast Cancer Res Treat

195

131

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“…Recently, we showed that the presence of CK19 þ disseminated tumour cells in the bone marrow by reverse transcriptase -PCR is an independent prognostic factor in untreated patients with breast cancer (Benoy et al, 2006). Moreover, a pooled analysis involving 4703 patients indicated that the presence of micrometastasis in the bone marrow at the time of diagnosis of breast cancer is an independent predictor of poor prognosis (Braun et al, 2005).…”

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confidence: 99%

The presence of circulating total DNA and methylated genes is associated with circulating tumour cells in blood from breast cancer patients

et al. 2009

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Circulating tumour cells (CTC) and tumour-related methylated DNA in blood have been separately assessed for their utility as a marker for subclinical metastasis in breast cancer. However, no studies have looked into the relation between the both molecular markers in this type of cancer. In this study, we investigated the correlations between total/methylated DNA and CTC in the blood from metastatic breast cancer patients. We simultaneously obtained whole blood, plasma and serum samples from 80 patients and 20 controls. The CellSearch System was used to enumerate CTC in blood samples. Plasma total DNA levels were determined by a QPCR method. Sera were analysed by methylation-specific QPCR for three markers: adenomatous polyposis coli (APC), ras association domain family protein 1A (RASSF1A) and oestrogen receptor 1 (ESR1). Total DNA levels in patients were significantly increased when compared with controls (Po0.001) and correlated with the number of CTC (r ¼ 0.418, Po0.001). Hypermethylation of one or more genes was detected in 42 (53%) serum samples from breast cancer patients and in three (16%) serum samples from controls (P ¼ 0.003). APC was hypermethylated in 29%, RASSF1A in 35% and ESR1 in 20% of breast cancer cases. Detection of a methylated gene in serum was associated with the detection of CTC in blood (P ¼ 0.03). The detection of large amounts of circulating total/ methylated DNA correlated with the presence of CTC in the blood from patients with breast cancer. This can be interpreted in two ways: (a) CTC are a potential source of circulating tumour-specific DNA; (b) high numbers of CTC and circulating methylated DNA are both a phenotypic feature of more aggressive tumour biology.

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“…Traditional prognostic factors do not accurately predict which patients will eventually relapse after primary treatment, and provide only limited information on the effectiveness of adjuvant treatment. Accumulating reports show that the detection of circulating tumour cells (CTCs) in body fluids has considerable potential to improve the clinical management of patients with breast cancer (Cristofanilli et al, 2004(Cristofanilli et al, , 2005Budd et al, 2006;Hayes et al, 2006;Wong et al, 2006;Benoy et al, 2006a;Rack et al, 2009). Over the past few years, different approaches for the detection, enumeration and isolation of CTCs in blood have been developed.…”

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confidence: 99%

Circulating tumour cell detection: a direct comparison between the CellSearch System, the AdnaTest and CK-19/mammaglobin RT–PCR in patients with metastatic breast cancer

Auwera

Peeters

Benoy³

et al. 2009

Br J Cancer

166

107

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BACKGROUND: The detection, enumeration and isolation of circulating tumour cells (CTCs) have considerable potential to influence the clinical management of patients with breast cancer. There is, however, substantial variability in the rates of positive samples using existing detection techniques. The lack of standardisation of technology hampers the implementation of CTC measurement in clinical routine practice. METHODS: This study was designed to directly compare three techniques for detecting CTCs in blood samples taken from 76 patients with metastatic breast cancer (MBC) and from 20 healthy controls: the CellSearch CTC System, the AdnaTest Breast Cancer Select/ Detect and a previously developed real-time qRT-PCR assay for the detection of CK-19 and mammaglobin transcripts. RESULTS: As a result, 36% of patients with MBC were positive by the CellSearch System, 22% by the AdnaTest, 26% using RT -PCR for CK-19 and 54% using RT -PCR for mammaglobin. Samples were significantly more likely to be positive for at least one mRNA marker using RT -PCR than using the CellSearch System (P ¼ 0.001) or the AdnaTest (Po0.001). CONCLUSION: We observed a substantial variation in the detection rates of CTCs in blood from breast cancer patients using three different techniques. A higher rate of positive samples was observed using a combined qRT-PCR approach for CK-19 and mammaglobin, which suggests that this is currently the most sensitive technique for detecting CTCs.

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Prognostic Significance of Disseminated Tumor Cells as Detected by Quantitative Real-Time Reverse-Transcriptase Polymerase Chain Reaction in Patients with Breast Cancer

Cited by 29 publications

References 20 publications

Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients

Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients

The presence of circulating total DNA and methylated genes is associated with circulating tumour cells in blood from breast cancer patients

Circulating tumour cell detection: a direct comparison between the CellSearch System, the AdnaTest and CK-19/mammaglobin RT–PCR in patients with metastatic breast cancer

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