Metabolism and breast cancer risk: frontiers in research and practice

Abstract

Fifty years ago the causes of cancer were largely unknown. Since then, it has become clear that a strong relationship exists between obesity and many cancers, particularly postmenopausal breast cancer. A major challenge in understanding the link between obesity and cancer risk has been elucidating the biological basis underlying the association. Although this remains unresolved, the main candidate systems linking adiposity and cancer risk are insulin and the insulin-like growth factor-1 axis, endogenous reproductive hormones, and chronic inflammation. Our purpose is to provide a mechanistic overview of the hypothesized relationship between diet, physical activity, and obesity with breast cancer risk and progression. In addition, we will provide examples of recently funded randomized clinical trials examining metabolic risk factors in relation to breast cancer risk and survival. Additional research is warranted to validate the strength and consistency of the relationships among diet, these biomarkers, and breast cancer risk. As these relationships become clearer, future studies will be needed to develop effective intervention programs to prevent breast cancer and improve cancer prognosis by promoting a healthy lifestyle.

Figure 1

A Proposed Mechanistic Model in Which the Shaded Boxes Represent Pathways Hypothesized to Link Excess Adiposity (defined as BMI ≥ 25 kg/m²), Insulin Resistance, and Other Metabolic Factors with Cancer Risk (either Incidence or Recurrence). Abbreviations: NF-κB=nuclear factor κB; IKKβ=IκB kinase β; PPARs= peroxisome proliferator-activated receptors; FFA=free fatty acids; TNF-α=tumor necrosis factor-alpha; GH=growth hormone; IGF=insulin-like growth factor; IGFBP=insulin-like growth factor binding protein; GHBP=growth hormone binding protein. Keys: ↑, increase in circulating concentrations; ↓ decrease in circulating concentrations.