The potential contribution of dietary factors to breast cancer prevention

Abstract

Breast cancer (BC), the leading cancer in women, is increasing in prevalence worldwide, concurrent with western metabolic epidemics, that is, obesity, metabolic syndrome, and diabetes, and shares major risk factors with these diseases. The corresponding potential for nutritional contributions toward BC prevention is reviewed and related to critical stages in the life cycle and their implications for carcinogenic and pathometabolic trajectories. BC initiation potentially involves diet-related pro-oxidative, inflammatory, and procarcinogenic processes, that interact through combined lipid/fatty acid peroxidation, estrogen metabolism, and related DNA-adduct/depurination/mutation formation. The pathometabolic trajectory is affected by high estrogen, insulin, and growth factor cascades and resultant accelerated proliferation/progression. Anthropometric risk factors - high birth weight, adult tallness, adiposity/BMI, and weight gain - are often reflective of these trends. A sex-based nutritional approach targets women's specific risk in western obesogenic environments, associated with increasing fatness, estrogen metabolism, n-6 : n-3 polyunsaturated fatty acid ratio, and n-6 polyunsaturated fatty acid conversion to proinflammatory/carcinogenic eicosanoids, and effects of timing of life events, for example, ages at menarche, full-term pregnancy, and menopause. Recent large-scale studies have confirmed the effectiveness of the evidence-based recommendations against BC risk, emphasizing low-energy density diets, highly nutritious plant-based regimes, physical activity, and body/abdominal adiposity management. Better understanding of dietary inter-relationships with BC, as applied to food intake, selection, combination, and processing/preparation, and recommended patterns, for example, Mediterranean, DASH, plant-based, low energy density, and low glycemic load, with high nutrient/phytonutrient density, would increase public motivation and authoritative support for early/timely prevention, optimally merging with other dietary/health goals, for lifelong BC prevention.

Fig. 1

Olive oil as a naturally occurring ‘anti-human epidermal growth factor receptor 2 (HER2) cocktail’. In terms of protective effects against breast cancer, olive oil has a very favorable fat composition as it appears to combine a new composite biomarker for breast cancer, that is, a low n-6 : n-3 polyunsaturated fatty acid (PUFA) ratio, and elevated n-9 monounsaturated fatty acid (MUFA) levels (Menendez et al., 2007).

Fig. 2

The mechanisms of action of aspirin (anticyclooxygenase products of arachidonic acid). Prostaglandin synthesis through arachidonic acid and the possible effects of cyclooxygenase inhibitors as chemopreventive agents of breast cancer by the intracellular accumulation of arachidonic acid, which directly promotes apoptosis and attenuation of positive feedback for proliferation and survival. COX, cyclooxygenase; COXIBs, COX2 selective inhibitors; PG, prostaglandin; TXA₂, thromboxane A₂ (Jacobo-Herrera et al., 2014).

Fig. 3

Proposed scheme for metabolic redox-cycling of 4-hydroxyestradiol leading to reactive oxygen species and lipid peroxidation (LPO) of ω-6 polyunsaturated fatty acid (PUFA); the resulting LPO byproducts such as 4-hydroxy-2-nonenal and malondialdehyde generate miscoding etheno-DNA adducts (edA and edC) and M1dG, respectively, that were analyzed in white blood cell of healthy female volunteers (Sun et al., 2012).