title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA. qkhan@kumc.edu.
authors.forename: Qamar J
authors.initials: QJ
authors.lastname: Khan
authors.forename: Bruce F
authors.initials: BF
authors.lastname: Kimler
authors.forename: Anne P
authors.initials: AP
authors.lastname: O'Dea
authors.forename: Carola M
authors.initials: CM
authors.lastname: Zalles
authors.forename: Priyanka
authors.initials: P
authors.lastname: Sharma
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Fabian
mesh_terms: D000328:Adult; D001706:Biopsy; D044963:Biopsy, Fine-Needle; D001940:Breast / Q000166:cytology* / Q000473:pathology; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D015914:Estrogen Replacement Therapy; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006965:Hyperplasia; D019394:Ki-67 Antigen / Q000235:genetics*; D008327:Mammography / Q000379:methods*; D008875:Middle Aged; D017698:Postmenopause; D017697:Premenopause; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: D019394:Ki-67 Antigen