CellSearchTM' Circulating Tumor Cells, Breast Cancer |
|
Test Summary |
|
Clinical Use
| • | Predict progression-free survival (PFS) and overall survival (OS) in patients with metastatic breast cancer |
Clinical Background
Circulating tumor cells (CTCs) are extremely rare in healthy individuals and patients with nonmalignant diseases but are present in patients with various metastatic carcinomas with a wide range of frequencies.1-2 Some clinical studies indicate the assessment of CTCs can assist physicians in monitoring and predicting cancer progression and in evaluating response to therapy in patients with metastatic cancer.3-5
In patients with metastatic breast cancer, the number of CTCs has been shown to be a significant predictor of progression-free survival (PFS) and overall survival (OS).6,7 In a study by Cristofanilli et al,7 patients undergoing treatment for metastatic breast cancer with >5 CTCs/7.5 mL whole blood had shorter median PFS (2.7 months vs 7.0 months, P<0.001) and shorter OS (10.1 months vs >18 months, P<0.001) than patients having <5 CTCs/7.5 mL blood. In the same study, a decrease in the number of CTCs to <5 from baseline to first follow-up (4-5 weeks after initiation of new therapy) was also found to be predictive of PFS and OS. These results suggest the number of CTCs is a useful prognostic guide for patients with metastatic breast cancer and can reliably estimate disease progression and survival earlier (4-5 weeks vs 8-12 weeks, respectively) than traditional imaging methods.
Individuals Suitable for Testing
Patients with metastatic breast cancer, prior to a new course of therapy and at follow-up.
Specimen Requirements
| • | 10 mL room temperature whole blood collected in CellSave Preservative Tube™'; 7.5 mL minimum. |
| • | Ship promptly; specimen must be tested within 72 hours of collection. Provide sample collection date and time. Do not refrigerate. |
| • | Samples may be collected prior to therapy and at first follow-up visit (4-5 weeks after initiation of new therapy). Allow at least 7 days after administration of doxorubicin before sample collection. |
Method
| • | Immunomagnetic sample enrichment using antibodies targeting epithelial cell adhesion molecule (EpCAM) and cell labeling with fluorescent nucleic acid dye |
| • | Epithelial cells distinguished from leukocytes using fluorescent labeled monoclonal antibodies specific for leukocytes (CD-45) and epithelial cells (cytokeratins 8,18, and 19) |
| • | Results reported as number of CTCs/7.5 mL of whole blood |
| • | Analytical sensitivity: 1 CTC/7.5 mL whole blood |
| • | Analytical specificity: 99.7%2 |
| • | Aliases: Breast Cancer CellSearch |
CPT Codes:* 88346 x2, 88361
Reference Range
Less than 5 CTCs/7.5 mL whole blood.
Interpretive Information
As shown in the table, a CTC count >5/7.5 mL prior to therapy or at first follow-up is predictive of shorter PFS and OS. A decrease in the number of CTCs to <5/7.5 mL from baseline to first follow-up is associated with longer PFS and OS.7
Prediction of Survival Based on Circulating Tumor Cell Count7
|
|
|
|
| CTC Count (# CTCs/7.5mL blood) | PFS (months) | OS (months) | |
 |
|||
| Prior to therapy | |||
| <5 | 7 | >18 | |
| >5 | 2.7 | 10.1 | |
| Baseline and first follow-up | |||
| <5 | 6.1 | >18 | |
| >5 | 1.3 | 7 | |
| First follow-up | |||
| Both <5 | 7 | >18 | |
| Baseline >5; follow-up <5 | 7.6 | 14.6 | |
| Both >5 | 2.1 | 8.2 | |
|
|||
| CTC, circulating tumor cell; PFS, progression-free survival; OS, overall survival. | |||
Antibodies used in the CellSearch assay are targeted at cell markers (EpCAM and cytokeratins 8, 18, and 19) expressed by adenocarcinomas.
Online Resources for Healthcare Professionals
| • | Access our online Test Menu |
| • | Access our Interpretive Guide |
| • | Simplify test ordering and results reporting with Care360™ |
Online Test Information for Your Patients
Your patients can learn about health conditions and laboratory tests in our online Patient Health Library. The library is founded on evidence-based information, provides printer friendly formats, and includes topics such as:
Contact a Quest Diagnostics Sales Representative, learn more about our testing services, and become a client
| • | Contact a physician sales representative |
| • | Contact a hospital sales representative or learn about our complete hospital offerings |
* The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed.
References
1 Molnar B, Sipos F, Galamb O, et al. Molecular detection of circulating cancer cells. Dig Dis. 2003;21:320-325.
2 Allard WJ, Matera J, Miller MC, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004;10:6897-6904.
3 Aquino A, Prete SP, Balduzzi A, et al. A novel method for monitoring response to chemotherapy based on the detection of circulating tumor cells: a case report. J Chemother. 2002;14:412-416.
4 Katoh M, Neumaier M, Nezam R, et al. Correlation of circulating tumor cells with tumor size and metastatic load in a spontaneous lung metastasis model. Anticancer Res. 2004;24:1421-1425.
5 Berrepoot LV, Mehra N, Vermaat JS, et al. Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients. Ann Oncol. 2004;15:139-145.
6 Weigelt B, Bosma AJ, Hart AA, Rodenhuis S, et al. Marker genes for circulating tumour cells predict survival in metastasized breast cancer patients. Br J Cancer. 2003;88:1091-1094.
7 Cristofanilli M, Budd T, Ellis M, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781-791.
8 Osta W, Chen Y, Mikhitarian K, et al. EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Research. 2004;64:5818-5824.
9 Armstrong A, Eck S. EpCAM: A new therapeutic target for an old cancer antigen. Cancer Biology & Therapy. 2003;2:320-326.
10 Gaforio JJ, Serrano MJ, Sanchez-Rovira P, et al. Detection of breast cancer cells in the peripheral blood is positively correlated with estrogen-receptor status and predicts for poor prognosis. Int J Cancer. 2003;107:984-990.
11 Abd El-Rehim DM, Pinder SE, Paish CE, et al. Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathol. 2004;203:661-671.
