Researchers at the M.D. Anderson Cancer Center, part of the University of Texas in Houston have found that circulating tumor cells (CTCs) can predict early recurrence and decreased overall survival in nonmetastatic breast cancer patients who have not yet been treated with chemotherapy. The results of the prospective trial are published this week in the Lancet Oncology. The trial is the largest to show the utility of CTCs as a way to predict breast cancer outcome in patients.
Anthony Lucci, MD, and colleagues aimed to understand whether measuring CTCs can predict worse outcomes in earlier stage breast cancer patients. CTCs have been linked to a worse prognosis in breast cancer patients with metastatic disease but there is currently no robust data on CTCs in nonmetastatic patients—it is not known if CTCs can be used as a prognostic factor in early-stage breast cancer.
Lucci and colleagues “postulated that identification of circulating tumor cells within the blood would independently predict shorter survival, irrespective of axillary lymph node status or standard tumor markers,” according to the publication. Currently, patients with breast cancer are staged based on the size of their tumor, the status of their regional lymph nodes, and whether there is macroscopic presence of metastatic disease. Because as many as one-quarter of localized disease patients whose lymph nodes test negative for cancer will relapse after primary treatment, better ways to understand the breast cancer of patients and their risk for recurrence is crucial. Assessing microscopic disease, irrespective of lymph node involvement is something that the field has not been able to do well just yet.
The Study Design and Results
The trial enrolled 302 patients with stage I–III breast cancer who had not been treated with chemotherapy, but had their tumors removed from surgery. Patients’ lymph nodes, primary metastases, and staging were assessed and tumor samples were stained for estrogen and HER2 expression to characterize both the molecule subtype and the clinical stage of disease. Both blood and bone marrow samples were taken from patients prior to their breast cancer surgery. Patients were followed up for a median of 35 months.
CTC levels were measured using the Veridex CellSearch System that uses fluorescence-labeling technology to identify CTCs and enrich for these cells in patients’ blood samples.
Neither tumor size nor other primary tumor characteristics predicted the presence of CTCs, said Lucci. CTC presence predicted both decreased progression-free survival and early disease recurrence and overall survival. One or more CTCs were found in 24% of patients. Identification of one or more CTC could predict both progression-free survival and overall survival (P = .005). The progression-free survival rate in women with one or more CTC was 87% compared to 69% for women who had three or more CTCs detected.
The study provides further evidence for what has already been postulated about CTCs—that cells from primary tumors break away and enter the circulating blood stream, facilitating disease progression. Further research, including development of even better CTC-detecting systems, understanding the consequence of having multiple CTCs in circulation, and developing biomarkers to target CTCs is ongoing. Large, multicenter trials will also be necessary to establish how clinical practice should integrate CTC measurements into diagnosis and treatment of breast cancer.