Abstract P5-10-03: Estrogen, obesity and mammary morphology in a middle-aged rat model of menopause

Abstract

Abstract The risk of occurrence of breast cancer changes at menopause in women. Various studies propose an association between mammographic density and adipose tissue distribution in premenopausal and post-menopausal women. There is a positive correlation between mammographic density and visceral adiposity in post-menopausal women, but an inverse correlation of the two in premenopausal women. Similar findings have also been discovered in rodent models. To model the premenopausal and post-menopausal status in women, this study used a middle-aged ovariectomized (OVX) Sprague Dawley rat model, given 17b-estradiol (E2) or vehicle (VEH) capsule, E2-deprived rats. Rats were OVX at 11 mo, and given E2 or VEH for 3 or 6 mo. A subset of rats were initially given E2 or VEH for 3 mo, then switched to the opposite treatment for another 3 mo, to evaluate the importance of E2 timing/duration. Mammary tumorigenesis was monitored through the treatment. Tumors were surgically removed upon detection. Rats were euthanized at 14 months old (3 mo of treatment) or 17 months old (6 mo of treatment). The 4th mammary gland was whole mounted for mammarographic density studies and comparisions. Serum estradiol, progesterone and prolactin concentrations were measured. Our results showed: 1) Body weight and visceral fat significantly decreased in E2 compared to VEH treated rats. 2) Following 3 or 6 mo E2 treatment, 3/54 and 5/72 rats, respectively, developed palpable mammary tumors. By contrast, 0/54 and 1/72 rats developed palpable tumors following 3 or 6 mo VEH treatment. In the group given 3 mo VEH then switched to E2 for 3 mo, 2/18 rats developed tumors. 1/18 rats developed tumors in the group given 3 mo of E2 then switched to VEH for 3 mo. 3) Mammary gland whole mounts showed increased mammographic density and decreased fat pad in E2 treated group. 4) Serum prolactin concentration significantly increased in E2 compared to VEH treated rats at euthanization. These results suggest timing and duration of hormone treatments have differing effects on mammary morphology and tumorigenesis. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-10-03.