Expression of p53 and markers for apoptosis in breast tissue during long-term hormone therapy in cynomolgus monkeys

Am J Obstet Gynecol. 2005 Jul;193(1):58-63. doi: 10.1016/j.ajog.2004.11.056.


Objective: The purpose of this study was to analyze the expression of p53 and markers for apoptosis in breast tissue during long-term hormone therapy in cynomolgus monkeys.

Study design: Sixty oophorectomized macaques were randomized to receive tibolone, conjugated equine estrogens (CEE), CEE+medroxyprogesterone acetate (MPA), or no hormonal treatment. Breast tissue was collected at necropsy after 2 years, and stained for p53, p21, and cleaved caspase-3.

Results: Differences were seen between treatment groups. The expression of p53 and caspase-3 was significantly lower in tibolone-treated animals (P<.01). Levels of p53 and caspase-3 were lower in the combined treatment group (CEE+MPA) when compared to both estrogen only and control groups.

Conclusion: Alternative regimens for hormonal therapy seem to have different effects on p53 expression and apoptotic activity within the breast. A combined effect of increased proliferation and decreased apoptosis could be one possible mechanism to explain an increased risk for breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Biomarkers / metabolism
  • Caspase 3
  • Caspases / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Drug Administration Schedule
  • Drug Combinations
  • Estrogens / administration & dosage
  • Estrogens / therapeutic use
  • Estrogens, Conjugated (USP) / administration & dosage
  • Estrogens, Conjugated (USP) / therapeutic use
  • Female
  • Hormone Replacement Therapy*
  • Immunohistochemistry
  • Macaca fascicularis
  • Mammary Glands, Animal / metabolism*
  • Medroxyprogesterone Acetate / administration & dosage
  • Medroxyprogesterone Acetate / therapeutic use
  • Norpregnenes / administration & dosage
  • Norpregnenes / therapeutic use
  • Tumor Suppressor Protein p53 / metabolism*


  • Biomarkers
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Drug Combinations
  • Estrogens
  • Estrogens, Conjugated (USP)
  • Norpregnenes
  • Tumor Suppressor Protein p53
  • Medroxyprogesterone Acetate
  • Caspase 3
  • Caspases
  • tibolone