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Breast Cancer Patients' Persistent Fatigue
is real, may speed up Aging
Newswise, April 21, 2011 --The persistent
fatigue that plagues one out of every three
breast cancer survivors may be caused by one
part of the autonomic nervous system running
in overdrive, while the other part fails to
slow it down.
That imbalance of a natural system in the
body appears linked to the tiredness and
exhaustion that can burden cancer patients
as much as a decade after their successful
The effect is so great, researchers say,
that it may be a sign of accelerated aging
in fatigued patients, causing them to seem
as much as 20 years older compared with
patients who aren’t fatigued.
Those new research findings, just reported
in the journal Psychoneuroendocrinology, are
the latest from a three-decade-long study of
the impact that stress can have on the human
Christopher Fagundes, a postdoctoral fellow
at Ohio State University’s Institute of
Behavioral Medicine Research (IBMR), and
Janice Kiecolt-Glaser, a professor of
psychiatry and psychology and a member of
the IBMR, drew early data from a larger
ongoing study testing whether yoga can
combat continuing fatigue in breast cancer
They were looking for a new biomarker, a
signal that could point to the initial cause
of this fatigue. Their target was the
autonomic nervous system, that part of the
body that controls unconscious activities
like breathing, heartbeat, digestion and
such, which earlier research had indicated
might play a role.
The autonomic nervous system has two main
parts – the sympathetic and the
parasympathetic. The former is responsible
for what has become known as the
fight-or-flight response, a triggering of
short-term, energized activity. The latter
deals with opposite situations. It is the
resting phase, best recognized by the
sleepiness that may follow eating a big
While the sympathetic system is an energy
hog, the parasympathetic conserves energy,
and the two should remain in balance in
healthy individuals. The researchers were
looking for differences between fatigued and
non-fatigued cancer survivors.
“We started looking for biomarkers for
cancer-related fatigue,” Fagundes said.
“Other research has indicated that a
systemic inflammation through the body might
be a reliable biomarker for this.
“Sick people with inflammation become tired
and lethargic, which makes sense since their
bodies are using energy to fight off
infections. You can imagine that a
long-term, systemic inflammation, year-in
and year-out, might produce this fatigue.”
For the study, 109 women participated and
were placed in one of two groups – those who
reported long-term fatigue and those who
didn’t. The women varied from being two
months to two years after being treated for
Fatigue is a normal response to breast
cancer treatments like chemotherapy and
radiation therapy, but one-third or more of
breast cancer survivors report continued
debilitating fatigue long after treatment
After a short relaxation period, each woman
had blood drawn to establish a baseline
level for norepinephrine, a stress hormone
that served as an indicator of activity by
the sympathetic nervous system.
Each participant had to give a five-minute
speech before a two-person panel and then do
a series of verbal arithmetic problems aimed
at increasing stress levels. Additional
blood samples were taken immediately after
the stressor and then a half-hour later.
The norepinephrine levels rose as expected
from the baseline in both groups after the
stressful episode but the researchers were
surprised to see something different.
Regardless of the stressor, women who had
persistent fatigue showed higher levels of
norepinephrine than those who weren’t
“They had higher sympathetic activity and
lower parasympathetic activity,” Fagundes
said, an indication that other researchers
have suggested is a signal for inflammation.
The researchers also gauged another measure
in the study, the natural variability in
heart rate which decreases as a person ages.
A lessened heart rate variability (HRV) is
also an indicator of activity in the
parasympathetic, or “resting,” system.
“People who were fatigued had weaker
parasympathetic activity than those who
weren’t,” he said.
“One of the things we know best is that
exercise can enhance a person’s HRV,”
Kiecolt-Glaser said. “Exercise is also the
best documented treatment for fatigue, so
this all begins to make sense.
“Fatigue isn’t a symptom that should be
ignored. It’s a marker for other things that
might be going on,” she said. Higher
norepinephrine levels and lower HRV have
been linked to high blood pressure,
myocardial infarctions, strokes and
“When a cancer patient reports persistent
fatigue following treatment, it is something
that deserves attention. It may be a symptom
of other things that matter.”
Working with Fagundes and Kiecolt-Glaser on
the work were William Malarkey, Charles
Shapiro, David Murray, Beom Seuk Hwang, Jean
Philippe Gouin and Julian Thayer, all from
Ohio State; and John Sollers from the
University of Auckland.
The work was supported in part by the
National Institutes of Health and the
American Cancer Society.