The labeling/marker antibodies for this test are for generic epithelial cells (not specifically for cancer cells).  We should be cautious, skeptical, but helpful as to instances when this test is ordered. [back to breast cancer table of contents]

Dr. Lambert-Falls (and possibly others) began in 2005 to sometimes order tests for CTCs on breast cancer patients.  The samples are obtained as whole blood in a special (CellSave tube contains a cell fixative and an anticoagulant¹) 7.5 m/L Vacutainer-type tube provided by Quest, the sample then being forwarded to Quest Laboratories.    A Dec. 2004 issue of Clinical Cancer Research noted that breast cancer cases disease free for up to 20 yrs have blood positive for CTCs! And CTCs have been documented in the blood of patients since 1869.  It could be that the technology might be translated for use to other types of cancer in the future.

 Test Use:

A fairly frequent medical oncological dilemma is early identification of patients effectively responding to chemotherapy vs. those in whom continuation is futile.  Dr. Lambert-Falls indicates that this test is another surrogate line of evidence for treatment effectiveness/ineffectiveness in a breast cancer case.  Test measures indicating effectiveness of a current therapeutic regimen encourage both the patient and the oncologists to "stay the course". 

• Serum chemicals: LDH has long been a marker, elevations tending to reflect spontaneous tumor necrosis and post-chemotherapy tumor lysis.
• Serum tumor markers: Medical Oncologists have not used this very extensively in our lab; levels are said to "bounce around" too much for good clinical dependability.  Chemotherapeutically effective tumor lysis may cause elevation of tumor markers. 
• Imaging: not infrequently, the tumor silhouette will fail to shrink, even though it may be responding to chemotherapy. 
• CTCs: <5 cells per 7.5 mL (per Vacutainer tube full of blood) is better;  >5 is worse.

 Technical information

• Veridex (a Johnson & Johnson company) is the name of the company producing the CellSearch CTC kit; Immunocon makes the detection instrument designed to automate and standardize the capture, enrichment, identification and enumeration of rare cells of epithelial origin in peripheral blood. A qualified human must visually determine whether the cells are tumor cells or not. The charge (late 2005) for the test is $605.00.  [Quest Lab info]
• I've not found any coefficient of variation data; but it is somewhere noted that the test is dependable +/- 1 CTC per tube of blood.  Yet, it is touted to the market place as a "simple blood test."
• No one has yet determined...all other factors being equal...whether tumor cells ordinarily "shed" into blood at a steady rate or whether in irregularly-timed bursts (as with bacteria causing sepsis from such as an abscess or endocarditis...the reason blood cultures are obtained as 3 samples over a period of time).
• No one has determined whether cancer cell shedding has any relationship to patient mobility or immobility or to volume and predominant sites of the stage IV disease.
• While it seems reasonable that early knowledge of evidence of failure or success of therapy helps make a treatment adjustment sooner, no one has shown significant increases in length of quality life or duration of life.
• The sample is apparently good for a minimum¹ of 72 hours and is collected prior to starting chemotherapy and 4-5 weeks after chemotherapy begins. 
• Immunomagnetic enrichment of test sample from the whole blood sample and antibodies used are ck8, ck18, ck19, and CD45 (CD45 allows normalizing out of monocytes). 
• Test alias's: CTC, CTCs, CellSearch, and Breast Cancer Cell Search. 

  Basis for test use:

• This test is not proven and is not standard of care as of 11/05!
• A study of 177 new and Tx-failed patients from 20 medical centers was studied (NEJMed 351(8): 781-791, 19 August 2004): if >5 CTCs prior to chemo, 53% don't live another year.
• Another study of the 83 (of those 177, above) who were "Tx-failed" had a CTC test before start of a new chemotherapy regimen and after 4 weeks of treatment, data showed a notable (but, to me, trivial) increase in survival.  Amazingly, marketing touts this group as a "homogeneous group" of 83 (J. Clin. Onc. 1 March 2005).
• Breast cancer cases disease free, even as long as 20 years, are often positive for CTCs. (December 2004 issue of Clinical Cancer Research, a group at UT Southwestern Medical Center in Dallas) [statement]
• In late 2007, a report came out of 100 breast cancer cases being followed with CTCs about every 4-5 weeks after chemo and for as long as 2 years: those cases with <5 CTCs did best & those higher CTC levels had a 5-fold increased risk of progression. If less cytotoxicity in a case leaves cells < 5 per 7.5cc, you limit patient toxicity; if > than 5, you intensify your treatment².
• CTCs "have been documented since 1869, and discussed in over 1500 publications" (Veridex website). We remember a burst of excitement about CTCs in relationship to prostate cancers in the mid-1990s.

References:

1. CAP Today May 2006.
2. Liu MC, "Circulating tumor cells (CTC): A reliable predictor of treatment efficacy in metastatic breast cancer (MBC)",

   J Clin Oncol 26: 2008 (May 20 suppl; abstr 11018).