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Longtime Recirculating Tumor Cells in Breast Cancer Patients

only RBC lysis and no other enrichment apart from a single step of centrifugation, we detect considerable numbers of circulating epithelial cells in 92% of patients with breast or lung cancer and none in 97% of normal controls. Among 16 patients with complete continuous remission, 13 had detectable numbers of circulating epithelial cells which were significantly lower (P = 0.005) than in patients with metastatic disease. Meng et al. speculate that, due to the rapid turnover of circulating tumor cells with a half-life of 1 to 2.5 hours after surgery of the primary tumor, there must be remote tumors, feeding these cells into the circulation. In breast cancer patients, we observe an up to 1,000-fold increase in epithelial cells during the first 3 days after surgery (Fig. 1; 2 out of the now >50 cases). A considerable part of these cells then disappears after another 2 to 4 days, consistent with a rapid turnover of these initially appearing cells. Subsequently, however, the number of epithelial cells remains stable over long periods of time (>1 year, as shown below). The same is true for remnant circulating epithelial cells after completion of adjuvant therapy and after completion of neoadjuvant therapy and surgery (Fig. 2). Others have shown (3) that dormant tumor cells can be long-lived. This agrees with our observations that the number of circulating cells remains at identically high levels for long times without any indication of relapse in the absence of additional interventions. We therefore favor the hypothesis that part of the tumor cells detected in the blood belong to a population of resting, longtime recirculating dormant breast cancer (stem) cells.