Effects of an exercise and hypocaloric healthy eating intervention on indices of psychological health status, hypothalamic-pituitary-adrenal axis regulation and immune function after early-stage breast cancer: a randomised controlled trial

Abstract

Introduction: Many women experience emotional distress, depression and anxiety after a diagnosis of breast cancer. Psychological stress and depression have been associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation that may adversely affect immune system functioning and impact upon survival. This study investigated the effects of a lifestyle intervention on indices of psychological health status, HPA axis regulation and immune function in overweight women recovering from early-stage breast cancer treatment.

Methods: A total of 85 women treated for breast cancer 3 to 18 months previously were randomly allocated to a 6-month exercise and hypocaloric healthy eating program plus usual care or usual care alone (control group). Women in the intervention group received three supervised exercise sessions per week and individualized dietary advice, supplemented by weekly nutrition seminars. Depressive symptoms (Beck Depression Inventory version II: BDI-II), perceived stress (Perceived Stress Scale: PSS), salivary diurnal cortisol rhythms; inflammatory cytokines (IL-6 and Tumor necrosis factor-α), leukocyte phenotype counts, natural killer (NK) cell cytotoxicity and lymphocyte proliferation following mitogenic stimulation were assessed at baseline and 6-month follow up.

Results: Compared with the control group, the intervention group exhibited a reduction in depressive symptoms (adjusted mean difference, 95% confidence intervals (95% CI): -3.12, -1.03 to -5.26; P = 0.004) at the 6-month follow-up but no significant decrease in PSS scores (-2.07, -4.96 to 0.82; P = 0.16). The lifestyle intervention also had a significant impact on diurnal salivary cortisol rhythm compared with usual care alone, as evidenced by an increase in morning salivary cortisol at the 6-month follow-up (P <0.04), indicating a change in HPA axis regulation. Women in the control group had higher total leukocyte, neutrophil and lymphocyte counts in comparison to the intervention group at the 6-month follow-up (P ≤0.05), whereas there was no difference in NK cell counts (P = 0.46), NK cell cytotoxicity (P = 0.85) or lymphocyte proliferation responses (P = 0.11) between the two groups.

Conclusion: Our results show that the lifestyle intervention resulted in a reduction in depressive symptoms and a normalisation of HPA axis regulation. Such changes could have important implications for long-term survival in women recovering from early-breast cancer treatment.

Trial registration: Current Controlled Trials: ISRCTN08045231.

Figure 1

Diurnal salivary cortisol rhythm at baseline and 6-month follow-up. Values are medians with error bars representing semi-interquartile range (SIQR). *P = 0.03 for area under the curve (AUC) between groups.

Figure 2

Natural killer (NK) cell cytotoxicity and lymphocyte proliferation at baseline and 6-month follow-up. Top, NK cell cytotoxicity at different effector: target cell ratios. Values are medians, with error bars representing semi-interquartile range (SIQR). Bottom, lLymphocyte proliferation responses. Values are means with error bars representing standard error of the mean. PHA, phytohemagglutinin.