Circulating Tumor Cells Could Predict Survival in Early Breast Cancer

Detectable circulating tumor cells in early breast cancer patients can predict prognosis, according to a newly published study.

Detectable circulating tumor cells (CTCs) in early breast cancer patients can predict prognosis, according to a new study published in the Journal of the National Cancer Institute.

The presence of CTCs has previously been shown to indicate a poorer survival outcome in women with metastatic breast cancer. In the current study, detectable CTCs were associated with a poorer overall survival (P = .0002), breast cancer–specific survival (P = .008), and disease-free survival (DFS; P < .0001). The presence of CTCs was also found to be an independent prognostic marker for DFS (hazard ratio [HR] = 2.11; P < .0001) and overall survival (HR = 2.18; P = .002).

At 36 months, the probability of being disease-free was 88.1% for those women with detectable CTCs compared with 93.7% for women who had no detectable CTCs.

The presence of CTCs was assessed in 2,026 women with early-stage breast cancer prior to adjuvant therapy and in 1,492 women following chemotherapy, by Brigitte Rack, MD, of the department of gynecology and obstetrics, Klinikum Innenstadt, Ludwig-Maximilians-Universitaet Muenchen in Munich, and colleagues.

The women were all part of the randomized phase III SUCCESS (Simultaneous Study of Gemcitabine-Docetaxel Combination Adjuvant Treatment as Well as Extended Bisphosphonate and Surveillance) trial. CTC analysis was conducted using the CellSearch platform. All of the patients had average to high-risk early-stage breast cancer.

Prior to adjuvant chemotherapy, CTCs were detected in 21.5% of patients (435 of 2,026). There was no association with tumor size, grade, or hormone receptor status. After chemotherapy, 22.1% of patients (330 of 1,493) were positive for CTCs.

Women that were positive for CTCs both before and after adjuvant therapy had the worst DFS compared with women who had no detectable CTCs or those who only had detectable CTCs either prior to or after therapy. The women with at least five CTCs per 30 mL of blood had the worst DFS and overall survival prognoses (HR = 4.51 for DFS, HR = 3.60 for overall survival). At 36 months, among the patients with five or more detectable CTCs, 28.1% of patients had recurrent disease and 14.3% had died compared with 7.1% and 3.4% of patients with less than five detectable CTCs, respectively (P < .0001 and P = .005).

CTCs that remained following adjuvant chemotherapy were also a negative prognostic indicator for DFS.

“The results indicate that patient outcome was associated with the absolute number of CTCs because the hazard ratios consistently increased with increasing cutoff values,” the authors concluded.

According to the study authors, detection of CTCs at an initial breast cancer diagnosis may not have an impact on treatment decisions. But, the authors also stated that detection of CTCs following adjuvant chemotherapy may be useful in guiding treatment.

While the analysis includes a large cohort of patients, the follow-up of 36 months is rather short, wrote Arnold M. Schwartz, MD, PhD, and Norris Nolan, MD, both of the department of pathology at the George Washington University in Washington, DC, in an accompanying editorial.

“The authors have demonstrated that CTCs may provide clinical prognostic information in a large cohort of early breast cancer,” Schwartz and Nolan concluded. “Additional studies and clinical experience will be needed to show that CTC assessment as a biomarker will have a satisfactory cost–benefit ratio and provide useful information for the management of breast cancer patients.”