Circulating Tumor Cells

[Joe]

Immunicon Corporation to Present at 2006 San Antonio Breast Cancer Symposium

Posters Address Attributes of Circulating Tumor Cells


HUNTINGDON VALLEY, Pa.--(BUSINESS WIRE)--Immunicon Corporation (NASDAQ-GM: IMMC) will present three posters at the 29th Annual San Antonio Breast Cancer Symposium, the premier breast cancer educational and scientific event, December 13-17 at the Georgia Henry B. Gonzalez Convention Center, San Antonio, Texas. The posters will address Immunicon’s cellular analysis of circulating tumor cells (CTC) in patients with metastatic breast cancer; CTCs in patients following adjuvant therapy; and the assessment of tumor cells in blood and bone marrow and gene signatures in primary breast cancer.

Presentations will include:

Circulating tumor cells in post-adjuvant breast cancer patients. (Abstract # 1011)

Almokadem S, Leitzel K, Harvey HA, Bannon E, Ali SM, Miller C, Terstappen LWWM, Doyle GV, Lipton A. Session Info: Poster Session I: Detection and Diagnosis: Circulating Markers (5:00-7:00 PM)

Presentation Time: Thursday, December 14, 2006, 4:45 PM

Apoptosis and Bcl-2 expression in circulating tumor cells from women being treated for metastatic breast cancer. (Abstract # 5005)

Smerage JB, Doyle GV, Budd GT, Wicha MS, Schott AF, Blayney DW, Repollet M, Terstappen LWMM, Hayes DF. Session Info: Poster Session V: Detection and Diagnosis: Marrow and Blood Micrometastases (5:00-7:00 PM)

Presentation Time: Saturday, December 16, 2006, 5:00 PM

Comparison of tumor cell levels in blood and bone marrow to hormone receptor status and gene signatures in tissue in patients undergoing surgical resection of primary breast cancer. (Abstract # 5008)

Frazier TG, Flynn MB, Sieling BA, Herman M, Rao C, Gross S, Pierce M, Doyle GV, Terstappen LWMM. Session Info: Poster Session V: Detection and Diagnosis: Marrow and Blood Micrometastases (5:00-7:00 PM)

Presentation Time: Saturday, December 16, 2006, 5:00 PM

Following the conference, the Immunicon presentations will be posted on Immunicon’s Web site at http://www.immunicon.com (http://www.immunicon.com/). The CellSearch™ Circulating Tumor Cell Kit to capture, count and characterize CTCs from a blood test, was developed by Immunicon and is marketed by Veridex, LLC, a Johnson & Johnson company. Veridex will exhibit at booth #219 during the meeting. For more about the 2006 San Antonio Breast Cancer Symposium, visit http://www.sabcs.org/ (http://www.sabcs.org/).

About Immunicon Corporation

For more information, please visit www.immunicon.com (http://www.immunicon.com/).

[Shell]

Joe-

Do you think it is useful to get this test if we also do the her2 serum testing blood work? I got it some time ago, and my number was 0, but I have since progressed. However, I just started doing the her2 serum testing blood work, andplan to follow with that for awhile to see what it shows...

Thanks and regards,
Shell

[Adriana Mangus]

Shell:What's the purpose of the test? I get tested every 6 weeks CA2729 and that's the only one I get done. SHould I ask my onc about other tests? WHat is her2 serum? Thanks for your help.

[Shell]

Adriana-

sorry - i don't know how to do links, but here is some info on it...

Shell

Circulating tumor cells in blood indicate more aggressive breast cancer

19 Aug 2004http://www.medilexicon.com/images/blanktab.gif




Patients with advanced breast cancer (http://www.mlclick.com/mlcl.php?aid=8D0EB297EDAEBBCCA0EDDD90DD3B06A6&fwd=501572.aspx) who have more than five circulating tumor cells in the blood may have a more dangerous form of the disease, according to a study published in the Aug. 19 issue of The New England Journal of Medicine.

The pivotal study could lead to more tailored treatments that would spare some women from the most potent chemotherapy, or, conversely, recognize which patients need more aggressive therapy at the start of treatment, says the study's lead author Massimo Cristofanilli, M.D., associate professor in The University of Texas M. D. Anderson Cancer Center's Department of Breast Medical Oncology.

"This is the first time that we can actually stratify metastatic breast cancer (http://www.mlclick.com/mlcl.php?aid=8D0EB297EDAEBBCCA0EDDD90DD3B06A6&fwd=501572.aspx) patients based on their risk," says Cristofanilli. "When a physician assesses a woman with metastatic breast cancer (http://www.mlclick.com/mlcl.php?aid=8D0EB297EDAEBBCCA0EDDD90DD3B06A6&fwd=501572.aspx), it is very difficult to make an accurate prediction of her prognosis. Now we may know more about what the prognosis will be, based on a simple blood test and a new technology. One day we may be able to suggest to a patient - based on personal risk - a more aggressive treatment, a less aggressive treatment, or no treatment at all."

Metastasis is the most life-threatening aspect of cancer, says Cristofanilli. To metastasize, cancer cells must leave the site of the primary tumor, travel through the blood and proliferate in a new site. Until recently, doctors have not been able to reliably isolate circulating tumor cells in the blood. Within the last few years, several methods have been developed to label tumor cells with antibodies that can then be measured precisely, identifying even one tumor cell in a vial of blood.

The prospective multi-center trial was conducted at 20 institutions in the United States - including the Cleveland Clinic, Duke University, the University of Arizona, and the University of Michigan - with M. D. Anderson as the lead site. In total, 177 women with metastatic disease were enrolled either prior to starting initial therapy or when changing to a new course of treatment. Patients were first tested for circulating tumor cell counts prior to therapy, and then again at first follow-up approximately three to four weeks later.

In the first test, 49 percent, or 87 women, were found to have five or more circulating tumor cells per 7.5 milliliters of blood, the equivalent of one blood draw. These patients had significantly shorter progression-free survival (2.7 months versus seven months) and overall survival (10.1 months versus greater than 18 months) than women with fewer than five circulating tumor cells per blood draw.

At the follow-up visit, circulating tumor cells again were collected. Then, 30 percent of the women were found to have five or more circulating tumor cells per blood draw, indicating a portion of the study group responded to therapy. The difference in progression-free survival between the two groups remained consistent - 2.1 months for women with five or more circulating tumor cells versus seven months for women with less than five circulating tumor cells. Overall, survival in the women with more than five circulating tumor cells was 8.2 months, compared to greater than 18 months in the cohort with less than five circulating tumor cells.

Moreover, says Cristofanilli, the presence of cancer cells in the blood predicted prognosis more accurately than the site of metastatic disease or the presence of estrogen receptor on the tumor cells, thereby having even more potential to impact standard treatment and future research.

"You can see there is a difference in efficacy or benefit of treatment in women who are selected based on the presence of cells or not," says Cristofanilli. "The most obvious case is estrogen-receptor positive disease. Some doctors are reluctant to give these women a hormonal treatment at diagnosis, but would rather be safe and give chemotherapy, the most aggressive treatment. Utilizing this test, we may one day definitively tell estrogen-receptor positive women if they have a worse prognosis and that chemotherapy is the right approach. Or, for those with few or no circulating cells, it is safe to go ahead with hormonal treatment alone."

Cristofanilli and his M. D. Anderson colleagues have long been working with circulating tumor cell technology and were the first to recognize the potential prognostic implications of its detection in women with metastatic disease. At the 2003 annual American Association of Cancer Research meeting, they reported a preliminary analysis of 41 patients evaluated at M. D. Anderson. These initial observations are further validated by the report of the results of this multi-center trial.

Cristofanilli would like to see circulating tumor status used prospectively to group patients for future clinical trials. Other future plans, says Cristofanilli, are to collect the circulating tumor cells, look at gene expression and see how it is representative of the primary tumor - perhaps, then doing away the need for a biopsy in the metastatic setting with the ability to evaluate how the patient is responding to therapy. In addition, he would like to study the correlation of circulating tumor cells to how patients respond to various types with treatments.

"If you look carefully, patients who are considered to have similar disease by standard clinical criteria may in fact have tumors that have quite different biological characteristics," he says. "Some patients might do better no matter what they receive."

The diagnostic technology utilized in this study, the CellSearch(tm) System, is marketed by Veridex, LLC, a Johnson & Johnson company. It is the first of its kind to automate the detection and enumeration of circulating tumor cells in peripheral blood, and works by detecting cancer cells that detach from solid tumors and enter the blood stream. The test is not yet commercially available to patients; it is expected to be available in fall 2004.

Cristofanilli cautions that the information generated by the technology is a powerful tool for both patient and physicians and must be utilized with caution.

"The majority of women facing metastatic breast cancer (http://www.mlclick.com/mlcl.php?aid=8D0EB297EDAEBBCCA0EDDD90DD3B06A6&fwd=501572.aspx) want to know their prognosis - good or bad - but they are afraid of bad news," he says. "If we can discover in a newly diagnosed patient that tumor cells are already in the blood, both patient and physician would be aware that we are dealing with a more aggressive cancer that requires more aggressive treatment early on."

The study was funded by Immunicon Corp. of Huntingdon Valley, Pa.

Contacts: Laura Sussman
lsussman@mdanderson.org
713-745-2457
Stephanie Dedeaux
srdedeau@mdanderson.org
713-563-0000
University of Texas M. D. Anderson Cancer Center (http://www.mdanderson.org/)

[gdpawel]

Using the CellSearch technique that quantifies circulating tumor cells, German investigators have shown that neoadjuvant chemotherapy with paclitaxel (taxol) causes a massive release of cells into the circulation, while at the same time reducing the size of the tumor. The finding could help explain the fact that complete pathologic responses do not correlate well with improvements in survival.

Circulating tumor cells (CTCs) are cancer cells that have detached from solid tumors and entered the blood stream. This can begin the process of metastasis, the most life-threatening aspect of cancer. To metastasize, or spread cancer to other sites in the body, CTCs travel through the blood and can take root in another tissue or organ.

In the study, breast cancer patients undergoing neoadjuvant chemotherapy gave blood samples in which epithelial antigen-positive cells were isolated. Such cells are detected in most breast cancer patients but are rarely found in normal subjects. The investigators measured the levels of cirulating tumor cells before and during primary chemotherapy with several different cytotoxic agents.

What this recent study has shown is that in three different paclitaxel (taxol) containing regimens, as the tumor collapses (a clinical response, not cure), it produces the greatest release of circulating tumor cells. The study has not looked at any other combination regimens.

The tumor shrinks, but more cells are found in the circulation. This corresponds with a high pathologic complete response during paclitaxel treatment, but in the end, this is not reflected in improved survival. These cells are alive in the circulation. The results indicate that monitoring of circulating tumor cells can contribute to understanding of tumor-blood interactions and may provide a valuable tool for therapy monitoring in solid tumors.

The results of this kind of study are coming out slowly and quietly and indicate that taxol containing regimens didn't prolong survival over other more conventional and less expensive cytotoxic drugs. It may indeed give clincial response (tumor shrinkage), sometimes impressive, however, these are mostly short-lived and relapses after a response to taxanes (taxol) are often dramatic.

Even before the advent of the CellSearch technique, it had been observed in "cell death" cell culture assays, that there was an increase in the number of metabolic activity of mitochondria of the surviving cells from Taxol therapy, even in cases where the majority of the cells are being killed by Taxol. It may indeed give clinical response (tumor shrinkage), however, these are mostly short-lived and relapses after a response are often dramatic.

Even if one or more chemotherapy regimen is identified as being likely to work on a particular cancer, has the science advanced to tell us whether application of the chosen chemotherapy regimen will not cause other changes that also cause cancer to later return and perhaps be even harder to treat? Is it a case of chemotherapy being bad, in cases where it apparently works? Traditional chemotherapy is mutagenic (changes in form), you might kill off a whole lot of cancer, only to cause a mutation in the remaining cancer, such that the remaining cancer behaves in a more agressive fashion.

Cancers that are a product of these genetic mutations release cells from the usual controls of proliferation and survival, making them so much harder to fight it. Following this mutation, the cancer cells acquire the ability to proliferate without the normal restraints. As the cancer grows, it may infiltrate and destroy the surrounding tissue, and metastasize by penetrating into blood vessels, lymph nodes, and body cavities. Distant metastasis via the bloodstream may affect virtually any organ (the lungs, bones, liver, adrenals, and even the brain).

These studies tell us that much more work needs to be done, and oncologists need to adapt treatment to the patient. There are over 100 chemotherapeutic agents, all of which have approximately the same probability of working. The tumors of different patients have different responses to chemotherapy. It requires individualized treatment based on testing individual properties of each patient's cancer.

Source: (Oncol News Int'l, Vol 14, #5, May '05)