Estrogen Receptor Expression of DMBA‐Induced Mammary Tumors in Intact and Ovariectomized Lean and Obese Zucker Rats.

Abstract

Obesity is associated with increased risk for postmenopausal breast cancer. Clinical data suggest that women with Estrogen Receptor negative (ER−) breast cancer have poorer outcome than those with ER+ tumors. The main objective of this study was to investigate whether obesity can be associated with the expression of ER in mammary tumors in the presence or absence of ovarian estrogen. Lean and obese Zucker rats were sham operated or ovariectomized at age 40 days and were gavaged at age 50 days with 65 mg/kg DMBA. Rats were weighed and palpated twice weekly for detection of mammary tumors and killed 135 days post-DMBA treatment. ER immunohistochemistry was performed on paraffin-embedded tumors. The incidence of mammary tumors was 59% in the obese, sham-operated (O/S) rats compared to 30% in the lean sham-operated (L/S) group (P<0.05) and 36% for the obese ovariectomized (O/O) rats while no lean ovariectomized (L/O) rats developed tumors (P<0.001). ER expression was evaluated for all the ductal carcinoma in situ (DCIS) or invasive ductal and lobular carcinoma (IDC) tumors and the results are as follows; L/S group (17% ER – and 83% ER+), O/S group (45% ER− and 55% ER+) and O/O groups had 50% ER− and 50% ER +. These preliminary results suggest that obesity may increase the incidence of ER negative tumors in the obese Zucker rat DMBA mammary tumor model (Supported by Susan G. Komen Breast cancer foundation and ABI to RH)