Circulating Tumor Cells, Disease Progression, and Survival in Metastatic Breast Cancer

N Engl J Med. 2004 Aug 19;351(8):781-91. doi: 10.1056/NEJMoa040766.

Abstract

Background: We tested the hypothesis that the level of circulating tumor cells can predict survival in metastatic breast cancer.

Methods: In a prospective, multicenter study, we tested 177 patients with measurable metastatic breast cancer for levels of circulating tumor cells both before the patients were to start a new line of treatment and at the first follow-up visit. The progression of the disease or the response to treatment was determined with the use of standard imaging studies at the participating centers.

Results: Outcomes were assessed according to levels of circulating tumor cells at baseline, before the patients started a new treatment for metastatic disease. Patients in a training set with levels of circulating tumor cells equal to or higher than 5 per 7.5 ml of whole blood, as compared with the group with fewer than 5 circulating tumor cells per 7.5 ml, had a shorter median progression-free survival (2.7 months vs. 7.0 months, P<0.001) and shorter overall survival (10.1 months vs. >18 months, P<0.001). At the first follow-up visit after the initiation of therapy, this difference between the groups persisted (progression-free survival, 2.1 months vs. 7.0 months; P<0.001; overall survival, 8.2 months vs. >18 months; P<0.001), and the reduced proportion of patients (from 49 percent to 30 percent) in the group with an unfavorable prognosis suggested that there was a benefit from therapy. The multivariate Cox proportional-hazards regression showed that, of all the variables in the statistical model, the levels of circulating tumor cells at baseline and at the first follow-up visit were the most significant predictors of progression-free and overall survival.

Conclusions: The number of circulating tumor cells before treatment is an independent predictor of progression-free survival and overall survival in patients with metastatic breast cancer.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Breast Neoplasms / blood
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • Cell Separation
  • Disease Progression
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating*
  • Proportional Hazards Models
  • Prospective Studies
  • Survival Analysis