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However, poor adherence to continuous energy restriction (CER) means energy restriction is difficult to implement.

The aforementioned data suggest energy restriction would be useful for breast cancer prevention in overweight and obese women. Within the breast, in general there is downregulation of metabolic pathways associated with anabolism and upregulation of pathways associated with catabolism. For example, systemically, energy restriction is associated with reductions in insulin, leptin and inflammatory markers. This effect appears to be mediated by changes in a number of systemic factors and also local factors within breast cells. Multiple studies in rodent models also indicate that energy restriction reduces the risk of breast cancer.

In the Iowa Women’s Health Study, ≥5 % maintained weight loss resulted in 20–40 % reduction in postmenopausal breast cancer risk compared with women who continued to gain weight. Observational studies in women indicate that weight gain increases breast cancer risk and weight reduction decreases breast cancer risk. Corresponding gene changes were not seen in peripheral blood lymphocytes. These groups did not differ in the degree of changes in weight, total body fat, fat cell size or serum or urine metabolomic markers. There was no appreciable effect of IER on breast gene expression in the other nine subjects. Some of these women also had increases in genes associated with breast epithelial cell differentiation (secretoglobulins, milk proteins and mucins) and decreased collagen synthesis (TNMD, PCOLCE2, TIMP4). Eleven subjects (55 %) displayed reductions in energy restriction-associated metabolic gene pathways including lipid synthesis, gluconeogenesis and glycogen synthesis. Ninety-one percent of these returned to baseline after 5 days of normal eating.

Five hundred and twenty-seven metabolites significantly increased or decreased during the two restricted days of IER. Insulin resistance (homeostatic model assessment (HOMA)) reduced by 29.8 % (☑7.8 %) on the restricted days and by 11 % (☓4 %) on the unrestricted days of the IER.