Circulating Tumor Cells Predict Disease-Free Survival and Overall Survival in Patients With Early Average- to High-Risk Breast Cancer
Although presence of circulating tumor cells has been shown to predict reduced survival in metastatic breast cancer, data on their predictive performance in earlier breast cancer are lacking. In a study reported in the Journal of the National Cancer Institute, Rack et al found that presence of circulating tumor cells was associated with reduced disease-free survival and overall survival in patients with early average- to high-risk breast cancer who participated in the SUCCESS trial.
The SUCCESS trial compared three cycles of fluorouracil (5-FU)/epirubicin/cyclophosphamide followed by three cycles of docetaxel every 3 weeks vs three cycles of 5-FU/epirubicin/cyclophosphamide followed by three cycles of gemcitabine/docetaxel every 3 weeks in patients with stages pT1-T4, pN0-N3, M0 breast cancer. After chemotherapy, patients were randomly assigned to 2 or 5 years of zoledronic acid. Hormone receptor–positive women received endocrine treatment.
Study Details
In the current analysis, circulating tumor cells were analyzed in 2,026 patients with early breast cancer before adjuvant chemotherapy and in 1,492 patients after chemotherapy using the CellSearch System.
Circulating tumor cells were defined as nucleated cells expressing cytokeratin and lacking CD45 identified after immunomagnetic enrichment for cells expressing the epithelial-cell adhesion molecule. Patients were followed for a median of 35 months (range, 0–54 months).
Circulating tumor cells were detected prior to chemotherapy in 21.5% of patients, including 19.6% of node-negative and 22.4% of node-positive patients (P < .001). There was no association between detection of circulating tumor cells and tumor size, grade, or hormone receptor status. After chemotherapy, circulating tumor cells were found in 22.1% of patients.
Effect on Disease-Free Survival
Circulating tumor cells were detected in three patients (19%) with locoregional relapse and 35 patients (30%) with distant metastases. The presence of circulating tumor cells prior to chemotherapy was associated with significantly reduced 3-year disease-free survival (88.1% vs 93.7%, P < .0001) and distant disease-free survival (87.9% vs 94.2%, P < .001).
In a multivariable proportional hazards model, presence of circulating tumor cells was an independent prognostic factor for reduced disease-free survival (hazard ratio [HR] = 2.11, P < .0001), with other significant factors consisting of negative hormone receptor status, lymph node involvement, unfavorable grade, and tumor size > 2 cm. Analysis by nodal status showed that presence of circulating tumor cells was associated with significantly reduced disease-free survival in all node-positive subgroups (P < .01 for 1–3, 4–9, and ≥ 10 positive nodes) but with no difference in node-negative patients (P = .23).
Effect on Overall Survival
Circulating tumor cells were present in 40.9% of patients who died and 20.8% of survivors. A total of 4.6% of circulating tumor cell–positive patients vs 2.2% of circulating tumor cell–negative patients died of breast cancer. The presence of circulating tumor cells prior to chemotherapy was associated with significantly reduced 3-year breast cancer-specific survival (P = .008) and overall survival (93.2% vs 97.3%, P = .0002). In the multivariable proportional hazards model, the presence of circulating tumor cells remained a significant predictor of poor overall survival (HR = 2.18, P = .002).
Overall, prognosis was worst in patients with five or more circulating tumor cells/30 mL blood, with hazard ratios of 4.51 (95% confidence interval [CI] = 2.59–7.86) for disease-free survival and 3.60 (95% CI = 1.56-8.45) for overall survival.
Persistence of Circulating Tumor Cells
The presence of persisting circulating tumor cells after chemotherapy was associated with significantly reduced 3-year disease-free survival (85.9% vs 93.9%, HR = 1.124, P = .02) and a borderline significant reduction in 3-year overall survival (92.8% vs 97.6%, HR = 1.162, P = .06).
The investigators concluded, “These results suggest the independent prognostic relevance of circulating tumor cells both before and after adjuvant chemotherapy in a large prospective trial of patients with primary breast cancer.”
Brigitte Rack, MD, of Ludwig-Maximilians-Universitaet Muenchen, is the corresponding author for the Journal of the National Cancer Institute article.
The study was supported by AstraZeneca, Chugai, Lilly, Novartis, Sanofi-Aventis, and Veridex. For full disclosures of the study authors, visit jnci.oxfordjournals.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
