More tumour cells in the blood leads to quicker deterioration in women with breast cancer

Aug 18 2004

A new study of women with advanced breast cancer who have more tumor cells circulating in their blood deteriorate and die quicker than women with fewer of these cells, according to the researchers from the University of Michigan Comprehensive Cancer Center and other cancer centers throughout the country.

These researchers found that about half of 177 women in the study whose breast cancer had metastasized, or spread, and who were starting a new treatment had elevated levels of circulating tumor cells in their blood system. Investigators defined an elevated level as five or more tumor cells in a sample of blood.

Of those women, 30 percent still had higher numbers of circulating tumor cells three to five weeks after beginning a new treatment and their cancer progressed very rapidly compared to women whose tumor cell levels dropped during that time or who never had elevated circulating cell levels. The study was performed using a newly developed technology called CellSearchTM that isolates and characterizes these cells. Results of the study appear in this week's New England Journal of Medicine.

"Identifying the number of circulating tumor cells in patients with metastatic breast cancer, especially at the time of their first follow-up after starting new therapy, may provide an early, reliable indication of whether that therapy will be successful," says senior study author Daniel Hayes, M.D., clinical director of the Breast Oncology Program at the University of Michigan Comprehensive Cancer Center.

Survival rates for women with metastatic breast cancer are low, and the goal of treatment is to slow the tumor's growth and decrease its size so symptoms lessen. Currently, to determine if a therapy is effective, patients often must wait three to four months after beginning the treatment and then undergo a series of tests, including bone scans and X-rays.

If the technique used in this study is proven effective, doctors could determine within several weeks if the therapy is working, with only a routine blood draw for the patient.

When cancer spreads, or metastasizes, it travels through either the lymph channels or the bloodstream. By filtering the blood, researchers can identify the cancer cells, called circulating tumor cells, in transit. The CellSearchTM technique involves mixing a blood sample with iron particles coated with an antibody that attaches to epithelial cells like those found in breast tissue. The cells are further characterized with other antibodies that have been tagged with a fluorescent dye, so that the cancer cells can be easily distinguished and counted. Since epithelial cells are not typically found in blood, their presence suggests they are cancerous cells from the breast tissue. The CellSearchTM system was developed by Immunicon Corp. in Huntingdon Valley, Pa., and is marketed by Veridex, LLC, a Johnson & Johnson company.

Twenty centers across the country participated in the trial, which prospectively enrolled 177 women with breast cancer that had spread to other parts of the body. All the women in the study were beginning a new systemic treatment, such as chemotherapy or hormone therapy.

In a control group of 345 women without breast cancer, only 1 percent had any circulating tumor cells in their blood. In contrast, 61 percent of the women with metastatic breast cancer had two or more circulating tumor cells.

The researchers grouped the first 102 women with breast cancer into a training set, using them to set a cutoff level of circulating tumor cells for determining good or bad prognosis. Researchers determined a cutoff of five circulating tumor cells per 7.5 ml of blood to indicate an elevated number. The remaining 75 patients were then used to validate that cutoff. Survival rates were similar for the training and validation groups.

Half of the women with metastatic breast cancer had more than five circulating tumor cells per 7.5 ml of blood at the start of the study. The time till their cancer progressed was less than three months for these women, compared to almost seven months progression-free for women with fewer than five circulating tumor cells. The women also died sooner when tumor cell levels were above five: 10 months survival in the elevated group, compared to more than 18 months if levels were low.

When researchers followed up with these women three to four weeks later, only 30 percent had five or more circulating tumor cells, suggesting the therapy was effective. Again, the cancer worsened more quickly in women with higher tumor cell numbers, and these women had shorter survival than women whose levels started high but dropped below five at follow-up.

"Women whose circulating tumor cell levels dropped after starting a new therapy or those who had few to begin with fared much better. Women who had more than five at first follow-up were probably on an ineffective therapy," Hayes says. "Changing therapies may be indicated, but it's possible we're identifying the 25 percent to 30 percent of patients for whom no therapy is going to work."

Researchers are currently considering a follow-up study to assess whether changing therapies can improve outcomes. At the current time, circulating tumor cell levels should not be used as a standard test to change therapy, but they may be considered within the context of other clinical, radiographic and blood testing, says Hayes, a professor of internal medicine at the U-M Medical School. He also cautions that circulating tumor cells cannot be used as a screening test for breast cancer, nor does the study have any implications for women diagnosed with non-metastatic cancer.