Reduction in Proliferation With Six Months of Letrozole in Women on Hormone Replacement Therapy

Breast Cancer Res Treat. 2007 Nov;106(1):75-84. doi: 10.1007/s10549-006-9476-5. Epub 2007 Jan 13.


The objective of this study was to determine if 6 months of the aromatase inhibitor letrozole, administered to postmenopausal women taking a stable dose of hormone replacement remedy, would be safe and would modulate biomarkers of breast cancer risk. The intent was to reduce the proliferation marker Ki-67 while maintaining adequate systemic levels of estradiol so as to avoid perimenopausal symptoms. Postmenopausal women at high risk for development of breast cancer and taking a stable dose of estrogen or estrogen plus progestin were screened by random periareolar fine needle aspiration (RPFNA). To be eligible, the acquired breast epithelial cells had to be characterized as cytologic atypia or borderline atypia with > or =1,000 epithelial cells on the cytomorphology slide; plus > or =500 epithelial cells on a slide processed for Ki-67 immunocytochemistry. Forty-two women were enrolled in the one arm study and received 2.5 mg letrozole per day for 6 months, followed by repeat assessment of biomarkers. Ki-67 was reduced by a median relative value of 66%. There was no significant change in breast cell cytomorphology; ER weighted index score; serum estradiol, testosterone, or IGF-1:IGFBP-3 ratio; mammographic breast density, or frequency or severity of perimenopausal symptoms. Given the dramatic reduction in proliferation, the effect of letrozole on risk and response biomarkers should be explored further in a randomized, placebo-controlled Phase IIB breast cancer chemoprevention trial.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Anticarcinogenic Agents / adverse effects
  • Anticarcinogenic Agents / therapeutic use*
  • Aromatase Inhibitors / adverse effects
  • Aromatase Inhibitors / therapeutic use*
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Biopsy, Fine-Needle
  • Breast Neoplasms / chemically induced
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / prevention & control*
  • Cell Nucleus / drug effects
  • Cell Nucleus / pathology
  • Cell Proliferation / drug effects*
  • Down-Regulation
  • Estradiol / blood
  • Estrogen Replacement Therapy / adverse effects*
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins / blood
  • Insulin-Like Growth Factor I / metabolism
  • Ki-67 Antigen / metabolism
  • Letrozole
  • Mammography
  • Middle Aged
  • Nitriles / adverse effects
  • Nitriles / therapeutic use*
  • Pilot Projects
  • Postmenopause
  • Receptors, Estrogen / metabolism
  • Risk Assessment
  • Risk Factors
  • Testosterone / blood
  • Time Factors
  • Treatment Outcome
  • Triazoles / adverse effects
  • Triazoles / therapeutic use*


  • Anticarcinogenic Agents
  • Aromatase Inhibitors
  • Biomarkers
  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins
  • Ki-67 Antigen
  • Nitriles
  • Receptors, Estrogen
  • Triazoles
  • Testosterone
  • Estradiol
  • Insulin-Like Growth Factor I
  • Letrozole