Aromatase inhibitor exemestane as a single - agent has no established role in the treatment of premenopausal
breast cancer women. The aim of this study was to evaluate preventive effects of
exemestane in the model of premenopausal Nmethyl- N-nitrosourea - induced mammary
carcinogenesis in female rats.
Exemestane treatment begun 7 days prior to
carcinogen administration and continued next 12 weeks - till the end of experiment.
Exemestane was dietary administered in two concentrations of 1 mg / 1kg (EXE 1), or 10 mg/1 kg (EXE 10), respectively.
Exemestane increased the
tumor frequency by 80.5 % (P=0.034) in the group EXE 1 and by 61.5 % (P=0.045) in the group EXE 10 in comparison with control animals. In the group EXE 10, the incidence of mammary
tumors was increased by 11.5 % (P=0.31) and
tumor volume by 41.5 % (P=0.23), also the latency was shortened by 8 days (P=0.078) compared with controls. In the groups with
exemestane, changes in weights and histology of uterus and vagina were not found at the end of experiment.
Exemestane did not alter serum concentrations of
estradiol,
testosterone and
dehydroepiandrosterone. In the group EXE 10 in comparison with untreated animals,
exemestane decreased serum concentrations of
triacylglycerols by 9 % (P=0.032), total
cholesterol by 19.5 % (P=0.0002) and
cholesterol of low - density and
high - density lipoprotein fractions by 41 % (P<0.0001), or 21.5 % (P=0.0002), respectively. In the group EXE 1, the decrease in
cholesterol of
low-density lipoprotein fraction by 22.5 % (P=0.0005) was recorded. An increase in food intake (P=0.023) and
body weight gain (P=0.036) was found in the group EXE 10 compared with the control group (P<0.05). The present study points to apparent
tumor - promoting effects of dietary administered
exemestane in the model of premenopausal mammary
carcinogenesis in female rats.
Exemestane as a steroidal agent indicated androgenic effects on rat lipid metabolism in this experiment.