Anesthesia and Circulating Tumor Cells in Primary Breast Cancer Patients: A Randomized Controlled Trial.

BACKGROUND The effect of anesthetic drugs on cancer outcomes remains unclear. This trial aimed to assess postoperative circulating tumor cell counts-an independent prognostic factor for breast cancer-to determine how anesthesia may indirectly affect prognosis. It was hypothesized that patients receiving sevoflurane would have higher postoperative tumor cell counts. METHODS The parallel, randomized controlled trial was conducted in two centers in Switzerland. Patients aged 18 to 85 yr without metastases and scheduled for primary breast cancer surgery were eligible. The patients were randomly assigned to either sevoflurane or propofol anesthesia. The patients and outcome assessors were blinded. The primary outcome was circulating tumor cell counts over time, assessed at three time points postoperatively (0, 48, and 72 h) by the CellSearch assay. Secondary outcomes included maximal circulating tumor cells value, positivity (cutoff: at least 1 and at least 5 tumor cells/7.5 ml blood), and the association between natural killer cell activity and tumor cell counts. This trial was registered with ClinicalTrials.gov (NCT02005770). RESULTS Between March 2014 and April 2018, 210 participants were enrolled, assigned to sevoflurane (n = 107) or propofol (n = 103) anesthesia, and eventually included in the analysis. Anesthesia type did not affect circulating tumor cell counts over time (median circulating tumor cell count [interquartile range]; for propofol: 1 [0 to 4] at 0 h, 1 [0 to 2] at 48 h, and 0 [0 to 1] at 72 h; and for sevoflurane: 1 [0 to 4] at 0 h, 0 [0 to 2] at 48 h, and 1 [0 to 2] at 72 h; rate ratio, 1.27 [95% CI, 0.95 to 1.71]; P = 0.103) or positivity. In one secondary analysis, administrating sevoflurane led to a significant increase in maximal tumor cell counts postoperatively. There was no association between natural killer cell activity and circulating tumor cell counts. CONCLUSIONS In this randomized controlled trial investigating the effect of anesthesia on an independent prognostic factor for breast cancer, there was no difference between sevoflurane and propofol with respect to circulating tumor cell counts over time. : WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Anesthesia may contribute to the distant spread of cancer during surgical treatmentThe presence of circulating tumor cells has been independently associated with both a higher risk of disease recurrence and reduced survival in both nonmetastatic and metastatic breast cancer WHAT THIS ARTICLE TELLS US THAT IS NEW: The hypothesis that postoperative circulating tumor cell counts would be higher in primary breast cancer patients receiving sevoflurane anesthesia than in those receiving intravenous anesthesia with propofol was tested in a randomized controlled trial of 210 patientsThe type of anesthesia did not affect circulating tumor cell counts over time (median circulating tumor cell count/7.5 ml blood [interquartile range]: for propofol, 1 [0 to 4] at end of surgery (0 h), 1 [0 to 2] at 48 h, and 0 [0 to 1] at 72 h; and for sevoflurane, 1 [0 to 4] at 0 h, 0 [0 to 2] at 48 h, and 1 [0 to 2] at 72 h; rate ratio, 1.27 [95% CI, 0.95 to 1.71]).