Effect of Diets Containing Different Levels of Linoleic Acid on Human Breast Cancer Growth and Lung Metastasis in Nude Mice¹

The purpose of the study was to determine the effect of three different levels of dietary linoleic acid (LA) intake on the growth of MDA-MB-435 human breast cancer cells in the mammary fat pads of nude mice, and their metastasis to the lungs. These diets were isocaloric, and contained different mixtures of safflower (LA-rich) and coconut (saturated fatty acid-rich) oils to provide 23% (w/w) total fat, with 2, 8, and 12% (w/w) LA. A fourth group was fed a low-fat, 5% (w/w) corn oil diet. There were 25 mice in each dietary group. At necropsy, 12 weeks after the tumor cell injections, the primary tumor weights in the 12% LA (4.1 ± 2.7 g)- and 8% LA (3.5 ± 1.7 g)-fed groups were significantly greater (P < 0.05) than those fed the 2% LA diet (2.5 ± 1.5 g); they did not differ significantly from the weights of mammary fat pad tumors in the 5% corn oil-fed mice. The incidence of grossly visible pulmonary metastatic nodules was not significantly different between the 8 and 12% LA-fed mice, but was higher for both groups compared with the 2% LA-fed group (P < 0.05), with a similar trend in comparison with the 5% corn oil group. The mean total calculated volumes of the macroscopic metastases per tumor-bearing mouse were significantly greater in the 8 and 12% LA (157 ± 250.7 and 99.1 ± 140.0 mm³, respectively), compared with the 2% LA (23.3 ± 51.8 mm³)- and 5% corn oil (24.5 ± 35.1 mm³)-fed mice; all P < 0.05. Micrometastases were observed most frequently in the 5% corn oil and 2% LA dietary groups, but none of the differences were statistically significant. No differences were detected in the concentrations of prostaglandin E, leukotriene B₄, or 5-hydroxyeicosatetraenoic acid in tumors from mice fed the four different diets.