Circulating Tumor Cells Predict Outcome in Metastatic Breast Ca

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.

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Circulating tumor cells: silent predictors of metastasis

F1000Research ◽

10.12688/f1000research.11313.1 ◽

2017 ◽

Vol 6 ◽

pp. 1445 ◽

Cited By ~ 23

Author(s):

LanLan Zhou ◽

David T. Dicker ◽

Elizabeth Matthew ◽

Wafik S. El-Deiry ◽

R. Katherine Alpaugh

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Metastatic Disease ◽

Metastatic Breast ◽

Prognostic Indicator ◽

Disease Recurrence ◽

Curative Intent ◽

Early Detection Of Disease ◽

Mere Presence ◽

Intent To Treat

Circulating tumor cells (CTCs) were added to the arsenal of clinical testing in 2004 for three cancer types: metastatic breast, prostate, and colorectal cancer. CTCs were found to be an independent prognostic indicator of survival for these three diseases. Multiple enrichment/isolation strategies have been developed and numerous assay applications have been performed using both single and pooled captured/enriched CTCs. We have reviewed the isolation techniques and touched on many analyses. The true utility of a CTC is that it acts as a “silent” predictor of metastatic disease. The mere presence of a single CTC is an indication that disease has spread from the primary site. Comments and suggestions have been set forth for CTCs and cell-free DNA to be used as a screening panel for the early detection of disease recurrence and metastatic spread, providing the opportunity for early intervention with curative intent to treat metastatic disease.

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Significance of Circulating Tumor Cells Detected by the CellSearch System in Patients with Metastatic Breast Colorectal and Prostate Cancer

Journal of Oncology ◽

10.1155/2010/617421 ◽

2010 ◽

Vol 2010 ◽

pp. 1-8 ◽

Cited By ~ 379

Author(s):

M. Craig Miller ◽

Gerald V. Doyle ◽

Leon W. M. M. Terstappen

Keyword(s):

Prostate Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Treatment Options ◽

Venous Blood ◽

Metastatic Breast ◽

Cellsearch System ◽

Multicenter Studies ◽

Real Time Analysis ◽

Number Of Treatment

The increasing number of treatment options for patients with metastatic carcinomas has created a concomitant need for new methods to monitor their use. Ideally, these modalities would be noninvasive, be independent of treatment, and provide quantitative real-time analysis of tumor activity in a variety of carcinomas. Assessment of circulating tumor cells (CTCs) shed into the blood during metastasis may satisfy this need. We developed the CellSearch System to enumerate CTC from 7.5 mL of venous blood. In this review we compare the outcomes from three prospective multicenter studies investigating the use of CTC to monitor patients undergoing treatment for metastatic breast (MBC), colorectal (MCRC), or prostate cancer (MPC) and review the CTC definition used in these studies. Evaluation of CTC at anytime during the course of disease allows assessment of patient prognosis and is predictive of overall survival.

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