Circulating tumor cells in blood indicate more aggressive breast cancer


Prognostic blood test may one day spare some patients toxic chemotherapy, offer others necessary aggressive frontline treatment

HOUSTON - Patients with advanced breast cancer 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 patients based on their risk," says Cristofanilli. "When a physician assesses a woman with metastatic breast cancer, 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 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."

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
    Published on All rights reserved.