Cyclin E and survival in patients with breast cancer

N Engl J Med. 2002 Nov 14;347(20):1566-75. doi: 10.1056/NEJMoa021153.


Background: Cyclin E, a regulator of the cell cycle, affects the behavior of breast-cancer cells. We investigated whether levels of cyclin E in the tumor correlated with survival among patients with breast cancer.

Methods: Tumor tissue from 395 patients with breast cancer was assayed for cyclin E, cyclin D1, cyclin D3, and the HER-2/neu oncogene with the use of Western blot analysis. Full-length, low-molecular-weight, and total cyclin E were measured. Immunohistochemical assessments of cyclin E were also made of 256 tumors. We sought correlations between levels of these molecular markers and disease-specific and overall survival.

Results: The median follow-up was 6.4 years. A high level of the low-molecular-weight isoforms of cyclin E, as detected by Western blotting, correlated strongly with disease-specific survival whether axillary lymph nodes were negative or positive for metastases (P<0.001). Among 114 patients with stage I breast cancer, none of the 102 patients with low levels of cyclin E in the tumor had died of breast cancer by five years after diagnosis, whereas all 12 patients with a high level of low-molecular-weight cyclin E had died of breast cancer within that period. In multivariate analysis, a high total cyclin E level or high levels of the low-molecular-weight forms of cyclin E were significantly correlated with poor outcome. The hazard ratio for death from breast cancer for patients with high total cyclin E levels as compared with those with low total cyclin E levels was 13.3--about eight times as high as the hazard ratios associated with other independent clinical and pathological risk factors.

Conclusions: Levels of total cyclin E and low-molecular-weight cyclin E in tumor tissue, as measured by Western blot assay, correlate strongly with survival in patients with breast cancer.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Blotting, Western
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology*
  • Cyclin D1 / analysis
  • Cyclin D3
  • Cyclin E / analysis*
  • Cyclins / analysis
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Proportional Hazards Models
  • Receptor, ErbB-2 / analysis
  • Retrospective Studies
  • Survival Analysis


  • CCND3 protein, human
  • Cyclin D3
  • Cyclin E
  • Cyclins
  • Cyclin D1
  • Receptor, ErbB-2