Identification of a chemoprevention cohort from a population of women at high risk for breast cancer

J Cell Biochem Suppl. 1996;25:112-22.


In a prospective pilot study, we performed breast fine needle aspirations (FNAs) on 213 high-risk and 30 low-risk women and analyzed these aspirates for cytologic changes and biomarker abnormalities of aneuploidy and overexpressed estrogen receptor (ER), epidermal growth factor receptor (EGFR), p53 and HER-2/neu. High-risk women were those with a first degree relative with breast cancer (73%), prior biopsy indicating premalignant breast disease (26%), a history of breast cancer (13%), or some multiple of these risk factors (11%). Median ages of the high-risk and low-risk groups were 44 and 42, respectively. Sixty-three percent of the high-risk and 73% of the low-risk group were premenopausal. Sixty-eight percent of the high-risk and 17% of low-risk women had cytologic evidence of hyperplasia with or without atypia (P < .0001). Aneuploidy and overexpression of EGFR and p53 occurred in 25%, 36%, and 28% of high-risk subjects but in less than 4% of low-risk subjects (P < .0002). Overexpression of ER and HER-2/neu occurred in 8% and 19%, respectively of high-risk women; nc low-risk women had these abnormalities. Sixty-eight percent of high-risk women and 7% of low-risk women had abnormalities of one or more of these biomarkers exclusive of cytology. Thirty-one percent of high-risk women, but no low-risk women had abnormalities of two or more biomarkers (P = .0004). Biomarker abnormalities were more frequent with increasing cytologic abnormality. Eighteen percent of women with normal cytology, 29% of women with epithelial hyperplasia and 60% of women with hyperplasia with atypia had abnormalities of two or more biomarkers (P = .048 and < .0001, respectively). Restricting the analysis to those three biomarkers most frequently overexpressed in the high-risk group (ploidy, EGFR, p53), 13% of high-risk women with normal cytology, 20% of high-risk women with epithelial hyperplasia and 51% of high-risk women with atypical hyperplasia had abnormalities of 2 or more of these 3 biomarkers. At a median follow up of two years, 8 of 213 women have been diagnosed with in situ (n = 5) or invasive (n = 3) cancer. Later detection of neoplasia was associated with prior FNA evidence of atypical hyperplasia (P < .0001) and multiple biomarker abnormalities in the 5 test battery (P = .006) by univariate analysis. By multivariate analysis, development and/or detection of cancer was primarily predicted by atypical hyperplasia (P = .0047) and secondarily by multiple biomarker abnormalities (P = 0.021). Atypical hyperplasia, EGFR, and p53 in breast FNAs have promise as risk markers and as surrogate endpoint biomarkers for breast cancer chemoprevention trials.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aneuploidy
  • Biomarkers, Tumor / analysis*
  • Biopsy, Needle
  • Breast / chemistry
  • Breast / pathology
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / pathology
  • Breast Neoplasms / prevention & control*
  • Chemoprevention
  • Cohort Studies
  • ErbB Receptors / analysis
  • Female
  • Humans
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Receptor, ErbB-2 / analysis
  • Receptors, Estrogen / analysis
  • Risk Factors
  • Tumor Suppressor Protein p53 / analysis


  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Tumor Suppressor Protein p53
  • ErbB Receptors
  • Receptor, ErbB-2