Neoplastic effects of exemestane in premenopausal breast cancer model.
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.
Kubatka
P
P
Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic. kubatka@jfmed.uniba.sk
Sadlonova
V
V
Kajo
K
K
Machalekova
K
K
Ostatnikova
D
D
Nosalova
G
G
Fetisovova
Z
Z
D000730:Androstadienes / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008770:Methylnitrosourea; D009929:Organ Size / Q000187:drug effects; D017697:Premenopause; D051381:Rats; D017207:Rats, Sprague-Dawley
D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D008770:Methylnitrosourea; C056516:exemestane