Diets Rich in n-6 or n-3 Polyunsaturated Fatty Acids Combined with Exercise Influences Tumour Development in a Her-2 Breast Cancer Model

Background/Objectives: Dietary changes or increased physical activity to promote health accompanies breast cancer treatment to improve outcomes and prevent cancer recurrence. However, primary breast cancer prevention studies are limited and while there is a growing benefit to diet and exercise, the combinatory benefits of diet and exercise are limited. Therefore, the objective of this exploratory study was to determine the effects of exposure to diets high in n-3 or n-6 polyunsaturated fatty acids (PUFA) combined with exercise on mammary tumour development in female MMTV-neu(ndl)YD5 mice. Methods: Animals were fed maternal diets containing 10% safflower oil (n-6 PUFA-enriched) or 3% menhaden oil + 7% safflower oil (n-3 PUFA enriched) for 20 weeks (wks). Within diets, mice were further divided into sedentary control or exercise groups (n = 8-12). Exercised mice were run on a treadmill from 8 to 12 wks of age before tumours developed. Once tumours were detected, volume and multiplicity were measured throughout the study. Results: Mice consuming n-3 PUFA had reduced tumour volume by 55% (p < 0.001) and weight by 42% (p = 0.02) compared to mice fed n-6 PUFA. Exercised n-3 PUFA-fed mice experienced 10% longer tumour-free status (TD50) than their sedentary counterparts and 24% longer TD50 than sedentary mice fed the n-6 PUFA enriched diet (p = 0.001). Exercised n-6 PUFA-fed mice established tumours 11% sooner than their sedentary counterparts and developed the largest and greatest number of tumours throughout the study (p < 0.0001). Conclusions: Overall, diet quality plays a significant role in mammary tumour outcomes. The effect of exercise on tumour outcomes was not as clear, but this exploratory study highlights the need to consider the temporal trajectory of tumour development that impacts not only lifespan but healthspan.