Mammographic density does not correlate with Ki-67 expression or cytomorphology in benign breast cells obtained by random periareolar fine needle aspiration from women at high risk for breast cancer

Breast Cancer Res. 2007;9(3):R35. doi: 10.1186/bcr1683.


Background: Ki-67 expression is a possible risk biomarker and is currently being used as a response biomarker in chemoprevention trials. Mammographic breast density is a risk biomarker and is also being used as a response biomarker. We previously showed that Ki-67 expression is higher in specimens of benign breast cells exhibiting cytologic atypia that are obtained by random periareolar fine needle aspiration (RPFNA). It is not known whether there is a correlation between mammographic density and Ki-67 expression in benign breast ductal cells obtained by RPFNA.

Methods: Included in the study were 344 women at high risk for developing breast cancer (based on personal or family history), seen at The University of Kansas Medical Center high-risk breast clinic, who underwent RPFNA with cytomorphology and Ki-67 assessment plus a mammogram. Mammographic breast density was assessed using the Cumulus program. Categorical variables were analyzed by chi2 test, and continuous variables were analyzed by nonparametric test and linear regression.

Results: Forty-seven per cent of women were premenopausal and 53% were postmenopausal. The median age was 48 years, median 5-year Gail Risk was 2.2%, and median Ki-67 was 1.9%. The median mammographic breast density was 37%. Ki-67 expression increased with cytologic abnormality (atypia versus no atypia; P <or= 0.001) and younger age (<or=50 years versus >50 years; P <or= 0.001). Mammographic density was higher in premenopausal women (P <or= 0.001), those with lower body mass index (P < 0.001), and those with lower 5-year Gail risk (P = 0.001). Mammographic density exhibited no correlation with Ki-67 expression or cytomorphology.

Conclusion: Given the lack of correlation of mammographic breast density with either cytomorphology or Ki-67 expression in RPFNA specimens, mammographic density and Ki-67 expression should be considered as potentially complementary response biomarkers in breast cancer chemoprevention trials.

MeSH terms

  • Adult
  • Biopsy
  • Biopsy, Fine-Needle
  • Breast / cytology*
  • Breast / pathology
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cohort Studies
  • Estrogen Replacement Therapy
  • Female
  • Gene Expression Regulation
  • Humans
  • Hyperplasia
  • Ki-67 Antigen / genetics*
  • Mammography / methods*
  • Middle Aged
  • Postmenopause
  • Premenopause
  • Regression Analysis
  • Risk Factors


  • Ki-67 Antigen