Nervous System Imbalance May Cause Fatigue in Breast Cancer Survivors

The persistent fatigue and exhaustion plaguing some breast cancer survivors after successful treatment stems from a tug of war between the "fight-or-flight" and "resting" parts of the autonomic nervous system, with the former working overtime and the other unable to rein it in, a new study suggests. Researchers from Ohio State University split 109 women who had completed breast cancer treatment up to two years earlier into two groups -- those who did and didn't report long-term fatigue -- and tested their blood for a baseline level of norepinephrine, a stress hormone. Participants were then asked to give a five-minute speech and do a series of verbal math problems, both tasks aimed at increasing their stress levels. As expected, further blood tests showed that levels of norepinephrine -- associated with the "fight-or-flight" sympathetic nervous system -- rose in both groups after the stressful experience, researchers said. However, breast cancer survivors who experienced persistent fatigue had higher levels than those who weren't chronically tired. The study, released online in advance of publication in an upcoming print issue of the journal Psychoneuroendocrinology, was partially funded by the U.S. National Institutes of Health and the American Cancer Society. The findings are the most recent from a 30-year-long study about the effects of stress on the human body. The researchers used earlier data from a larger ongoing study looking at whether yoga can ward off continuing fatigue in breast cancer patients. "We're not sure if the fatigue is stress-induced. But certainly cancer is an extremely stressful life event," said study author Christopher Fagundes, a postdoctoral fellow at Ohio State University's Institute of Behavioral Medicine Research. "So those stressors might be contributing to those autonomic system changes." The autonomic nervous system is comprised of two main parts: The sympathetic system is responsible for the short-term energized activity known as the fight-or-flight response, while the parasympathetic system conserves energy in a resting phase. Fagundes and his colleagues found that breast cancer survivors experiencing chronic exhaustion -- which occurs in one-third of patients -- had an imbalance between the two systems, with higher activity in the sympathetic system, which prior research suggests is a signal for systemic inflammation. This finding was pivotal, since the researchers were searching for reliable biomarkers for cancer-related fatigue. Earlier research indicated that body-wide systemic inflammation may be such a signal. The researchers also observed that fatigued participants experienced lower heart rate variability (HRV), which has been linked to high blood pressure, heart attacks, strokes and diabetes. While inflammation has been linked to fatigue in other forms of cancer, Fagundes' study only gathered data on breast cancer patients. The study authors pointed out that more research is needed. "We cannot say with certainty that lower HRV or higher norepinephrine leads to great fatigue, or vice versa, a limitation of the study. It is possible that fatigued cancer survivors have [these levels] due to inactivity and deconditioning," they wrote in the report. "Fatigue is something we've known about for quite some time but we really don't know that much about it, so I think this adds to the literature," said Lee Jones, scientific director of Duke Cancer Institute's Center for Cancer Survivorship in Durham, N.C. "We don't see this [fatigue] as much with other cancer survivors," Jones added, noting that some breast cancer drugs may have a negative impact on long-term energy levels because they can be toxic to the heart. Fagundes said the ongoing exhaustion in some women may be a sign of accelerated body-wide aging, causing their systems to function as if they were 20 years older than patients who weren't fatigued. Jones noted that some of his prior research indicated a similar effect on fitness levels, with breast cancer survivors exhibiting about 30 percent lower levels of cardiovascular fitness as sedentary women of the same age. Chemotherapy is likely to blame, he said. Both Fagundes and Jones advocated exercise as a way of mitigating cancer-related fatigue and maintaining fitness levels during and after treatment. "Exercise is probably the best way to restore that balance," Fagundes said. "Obviously the goal is always to attenuate those negative effects."