A high protein moderate carbohydrate diet fed at discrete meals reduces early progression of N-methyl-N-nitrosourea-induced breast tumorigenesis in rats

Abstract

Breast cancer is the most prevalent cancer in American women. Dietary factors are thought to have a strong influence on breast cancer incidence. This study utilized a meal-feeding protocol with female Sprague-Dawley rats to evaluate effects of two ratios of carbohydrate:protein on promotion and early progression of breast tissue carcinomas. Mammary tumors were induced by N-methyl-N-nitrosourea (MNU) at 52 d of age. Post-induction, animals were assigned to consume either a low protein high carbohydrate diet (LPHC; 15% and 60% of energy, respectively) or a high protein moderate carbohydrate diet (HPMC; 35% and 40% of energy, respectively) for 10 wk. Animals were fed 3 meals/day to mimic human absorption and metabolism patterns. The rate of palpable tumor incidence was reduced in HPMC relative to LPHC (12.9 +/- 1.4%/wk vs. 18.2 +/- 1.3%/wk). At 3 wk, post-prandial serum insulin was larger in the LPHC relative to HPMC (+136.4 +/- 33.1 pmol/L vs. +38.1 +/- 23.4 pmol/L), while at 10 wk there was a trend for post-prandial IGF-I to be increased in HPMC (P = 0.055). There were no differences in tumor latency, tumor surface area, or cumulative tumor mass between diet groups. The present study provides evidence that reducing the dietary carbohydrate:protein ratio attenuates the development of mammary tumors. These findings are consistent with reduced post-prandial insulin release potentially diminishing the proliferative environment required for breast cancer tumors to progress.

Figure 1

Body Weights; Values represent Means ± SEM. * indicates significant difference (P > 0.05).

Figure 2

Tumor Incidence; Comparison of slopes of linear regression (P = 0.019); LPHC: y = 18.10x - 119.3, r² = 0.968; HPMC: y = 12.95x - 87.86, r² = 0.937.