EFFECTS OF DIETARY OMEGA-3-FATTY-ACIDS ON HUMAN BREAST-CANCER GROWTH AND METASTASES IN NUDE-MICE

Background: Diets rich in omega-6 polyunsaturated fatty acids stimulat e the growth and metastases of transplantable mammary carcinomas in ro dents, whereas fish oil-containing diets, rich in omega-3 fatty acids, suppress the growth of these mammary tumor cells. Purpose: This study was performed to evaluate the effect of a diet rich in menhaden fish oil on the growth and metastases of MDA-MB-435 human breast cancer cel ls in a mouse model system. Methods: Ninety female athymic nude mice ( Ncr-nu/nu) were fed a 23% (wt/wt) corn oil, omega-6 fatty acid-rich di et; after 7 days, 1 x 10(6) estrogen-independent MDA-MB-435 human brea st cancer cells were injected into a thoracic mammary fat pad. The 23% corn oil diet was continued for a further 7 days, after which the mic e were assigned randomly to one of three diets containing a total of 2 3% fat, but different proportions of corn oil and menhaden oil (diet C m: 18% corn oil and 5% menhaden oil, diet CM: 11.5% corn oil and 11.5% menhaden oil, and diet cM: 5% corn oil and 18% menhaden oil). Animal body weights and the surface area of the mammary fat pad tumors were r ecorded weekly. The mice were killed after 12 weeks on the experimenta l diets. Primary tumor surface areas and body weights were compared by unpaired Student's t tests, the incidence of lung metastases by the c hi-square test, and differences in the total volumes of lung metastase s by the nonparametric Mann-Whitney U test. Results: Tumor growth rate s in the mice of the group fed diet Cm were significantly greater than for mice of either of the two groups fed diets containing higher leve ls of menhaden oil. Of the mice with primary tumors, the incidence of macroscopic lung metastases was greater in those fed diet Cm, compared with those fed diet cM (57.7% versus 22.2%; P<.01), but not significa ntly different from the mice fed diet CM. When metastases did occur, t heir extent was significantly greater in mice fed diet Cm, compared wi th those fed diet cM (P<.001). Conclusion: These results indicate that a high-fat diet rich in omega-3 fatty acids can suppress human breast cancer cell growth and metastases in this mouse model system. Implica tion: Dietary intervention trials to reduce recurrence risk in the pos tsurgical breast cancer patient should take account not only of the le vel of fat consumed, but also its fatty acid composition.