Each year over 40,000 women die in the United States from metastatic breast cancer. Obese women have an increased risk of postmenopausal breast cancer. Estrogen levels are positively correlated with breast caner. It has been proposed that excess adipose tissue leads to increased levels of estrogen in postmenopausal obese women, thus increasing breast cancer risk.
Purpose of Study This study evaluated whether obesity influences estrogen receptor (ER) expression of tumors arising after menopause as well as the affects of obesity on postmenopausal behavior of tumors established both before and after menopause. An estrogen-rich obese environment is anticipated to support ER-positive tumors more than an estrogen-poor lean environment.
Methods Twenty-five rats genetically inclined toward obesity and 25 rats genetically inclined to slenderness were MNU treated at 50 mg/kg of body weight. After the establishment of palpable tumors, ovaries were removed to simulate menopause. Two groups of tumors were evaluated. One group regressed after ovariectomy (OVEX), indicating hormone dependence, and then recurred. Another group arose post-OVEX. Immunohistochemistry using a pan-ER antibody was performed to determine tumor ER status. ER staining was classified +0 to +3 according to the percentage of positive ER-positive (ER+) staining. Tumors with < 5% ER+ cells were designated +0, 5 to 25% ER+ cells were designated +1, 25 to 75% ER+ cells were designated +2, > 75% ER+ cells were designated +3.
Results Following OVEX, 26 tumors regressed in the lean group of rats and 20 regressed in the obese group. More tumors arose post-OVEX in the obese rats than in the lean rats (38 compared with 28), indicating that the post-OVEX background in obese rates was less supportive of tumor survival. Tumors that regressed after OVEX and then recurred in the obese group were more ER+ than those in the lean group, with average ER+ scores of 2.83 (n = 6) and 0.6 (n = 5), respectively. The ER status of tumors arising after OVEX is under investigation. These data indicate that obesity supports ER+ tumors consistent with adiposite production of estrogen.
Conclusion These findings suggest that obesity influences the clinical outcome of breast cancer.
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