Sympathetic and parasympathetic activity in cancer-related fatigue: more evidence for a physiological substrate in cancer survivors.

Fatigue is a notable clinical problem in cancer survivors, and understanding its pathophysiology is important. This study evaluated relationships between fatigue and both sympathetic and parasympathetic nervous system activity in breast cancer survivors. Norepinephrine and heart rate variability (HRV) were evaluated at rest, as well as during and after a standardized laboratory speech and mental arithmetic stressor. The participants, 109 women who had completed treatment for stage 0-IIIA breast cancer within the past two years, were at least two months post surgery, radiation or chemotherapy, whichever occurred last. Women who reported more fatigue had significantly higher norepinephrine and lower HRV before and after the stressor than their less fatigued counterparts. Fatigue was not related to treatment or disease variables including treatment type, cancer stage, time since diagnosis, and time since treatment. Importantly, the relationship between HRV and cancer-related fatigue was sizeable. Based on research that has demonstrated characteristic age-related HRV decrements, our findings suggest a 20-year difference between fatigued and non-fatigued cancer survivors, raising the possibility that fatigue may signify accelerated aging. Furthermore, lower HRV and elevated norepinephrine have been associated with a number of adverse health outcomes; accordingly, fatigue may also signal the need for increased vigilance to other health threats.