Outcome of primary-breast-cancer patients with micrometastases: a long-term follow-up study

Lancet. 1999 Jul 17;354(9174):197-202. doi: 10.1016/s0140-6736(98)10175-7.


Background: Bone-marrow micrometastases have been found in patients with primary breast cancer. We report long-term follow-up of women with primary breast cancer, diagnosed between 1981 and 1986, who had multiple aspirates taken at the time of initial surgery.

Methods: 350 women with primary breast cancer were examined immunocytochemically with antibody to epithelial membrane antigen. We investigated associations with various prognostic factors as well as the effect of micrometastases on relapse-free survival and overall survival.

Findings: At median follow-up of 12.5 years, 151 patients had metastatic disease and 136 patients had died from breast cancer. 10-year relapse-free and overall survival were 43.9% (95% CI 33.4-54.7) and 44.9% (34.2-55.9) in patients with micrometastases, and 62.7% (56.5-68.6) and 65.7% (59.4-71.5) in patients without micrometastases at presentation (p<0.001). For relapse-free survival and overall survival, allowing for tumour size, lymph-node status, and vascular invasion, the effect of micrometastases decreased and was no longer significant, with a hazard ratio of 1.09 (0.74-1.61) for relapse-free survival and 1.21 (0.84-1.75) for overall survival.

Interpretation: The presence of bone-marrow micrometastases in patients with primary breast cancer is associated with a shorter relapse-free survival and overall survival, but is not an independent prognostic factor. This immunocytochemical technique may be of value in patients for whom pathological tumour size and lymph-node status are unavailable (ie, patients receiving primary medical treatment).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow Neoplasms / secondary*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Risk Factors
  • Survival Analysis
  • Time Factors