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

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.