ASCO Breast: Circulating Tumor Cells Show Tumor Response and Relapse Risk

SAN FRANCISCO, Sept. 12 -- Circulating tumor epithelial cells may open a window on the response of breast cancer to adjuvant therapy and, possibly, the risk of relapse as well, researchers said.

A greater than 10-fold increase in circulating tumor cells was seen in 23% of patients toward the end of adjuvant therapy, and was associated with an 11-fold increase in relapse risk (P<0.0001) in a study presented at the American Society of Clinical Oncology's Breast Cancer Symposium.

Monitoring these circulating tumor cells "allows early identification of patients at risk for relapse" and could enable oncologists to modify therapy accordingly, said Katharina Pachmann, M.D., of the Friedrich Schiller-University Jena in Bayreuth, Germany.

Dr. Pachmann and colleagues studied circulating tumor cell levels in 158 consecutive breast cancer patients using a method called MAINTRAC analysis, for which she holds a patent.

The method involves collecting 1 mL of anticoagulated peripheral blood, which is then processed with an antibody to make epithelial cells fluoresce and run through laser scanning cytometry to count the number of live cells. This procedure was done before the start of adjuvant treatment and before each chemotherapy cycle to monitor changes.

The patients included 85% of those treated at a single center with the only exclusion criteria being lack of patient consent to draw blood samples. Participants predominantly had stage T1 or T2 breast cancer.

The researchers found that the baseline number of circulating tumor cells correlated with tumor size (correlation coefficient=0.621), "an indicator that cells are continuously released into the blood during tumor growth," Dr. Pachmann said.

Patients were treated according to their risk profiles with the combination of fluorouracil (Adrucil) and epirubicin (Ellence) with or without cyclophosphamide (Cytoxan) and paclitaxel (Taxol) or with CMF chemotherapy (cyclophosphamide, methotrexate and fluorouracil).

During therapy, about 30% of patients had relatively stable circulating tumor cell numbers from baseline to end of treatment. Two-thirds had at least an initial reduction in cell numbers during therapy.

One-third of patients had at least a 10-fold reduction in circulating epithelial tumor cell levels, which Dr. Pachmann said was considered a marginal response to therapy "which might fair equally well without therapy." About 10% of patients had more than a 10,000-fold reduction during adjuvant therapy.

But toward the end of treatment, circulating tumor cell numbers rose again for about 25% of patients, with levels increasing up to 30,000-fold over baseline levels.

Of those who had an increase in tumor cells in peripheral blood, about 30% did not relapse over the mean of 3.5 years of observation. However, Dr. Pachmann noted that among those with follow-up out to 4.5 years, all patients with a re-increase in circulating tumor cell numbers had a relapse.

Overall, 23% of patients relapsed. All but two of these patients had an increase in circulating epithelial cell numbers toward the end of therapy.

Although the method needs further validation and study, it could fill an important role in adjuvant therapy for oncologists, who currently have no way to monitor response to therapy, Dr. Pachmann said.

Another method for counting circulating epithelial tumor cells, called the CellSearch System, has been used by other researchers, although not to follow patients during therapy, she noted.

"In the future you may monitor every single patient during therapy and change therapy accordingly," she said. "We could spare patients that do not respond to therapy from unnecessary treatment."