Carcinogen-Induced Breast Cancer Prevention by Ingestion of Stearate.
Robert W Hardy, Eric Toline, Lynda M Evans, Renee Desmond, Arig Ibrahim-Hashim, Gene P Siegal. University of Alabama at Birmingham
Background: Dietary stearate has been previously shown to reduce breast cancer tumor & metastatic burden in an orthotopic mouse model. The goal of the study was to test the effectiveness of dietary stearate at inhibiting breast cancer development in a carcinogen induced breast cancer model. We selected the N-nitroso-N-methylurea (NMU) rat carcinogen induced model because it is direct acting, does not require host activation, and tumors generated exhibit histologic and endocrinologic features which resemble human breast cancer.
Design: Three diets were used; a 17% stearate diet, the key being that highly purified stearate was added directly to the diet, a linoleate diet containing 17% safflower oil as the source of linoleate (SF) and a low fat control diet (LF) with a reduced amount of fat (5%) from corn oil. Corn oil contains a mix of linoleate and oleic acids as the major components which are, coincidently the two major non-esterified fatty acids in human serum. All 3 diets had adequate essential fatty acids and were fed to female rats treated with NMU and followed out 100 days. The diets were initiated 1 week prior to receiving NMU.
Results: There was no difference in the weight of the rats among groups throughout the study. Approximately 40% fewer animals on the stearate diet developed palpable tumors compared to the control (n=30-35 animals/diet; p<0.05). No difference was observed among the 3 diets as to the time for first tumor appearance. Stearate decreased the average number of tumors per rat compared to the LF (n=30-35 animals per diet; p<0.05) and had less tumors per rat than the SF although this was not statistically significant. Dietary stearate significantly reduced tumor burden as defined as a decreased in tumor weight by ∼50% as compared to LF and SF (p<0.001) and large tumors as compared to the LF (∼47% reduction in tumors over 0.25 g, p= 0.02). Stearate had similar results compared to the linoleate diet in terms of reduced numbers of large tumors; however they were not statistically significant. In those rats that did develop tumors, the stearate diet group had a similar number of adenocarcinomas compared to other diets; however the stearate and SF groups had lower numbers of DCIS/microinvasive disease as compared to the LF. The dietary groups had similar numbers of the other precursor lesions classified.
Conclusions: The stearate and SF diets were both effective at reducing both tumor burden and incidence in this model although stearate was the best at reducing tumor burden. Dietary stearate may be useful as an alternative/complementary therapy or preventative agent against breast cancer.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 228, Wednesday Morning