Vagal Tone, Cortisol Levels Linked to Sleep Disruption in Breast Cancer Patients

Sleep disruption is up to 3 times more common in cancer patients. Preliminary results from a recent study indicate that there is an association between disrupted sleep, lower heart rate variability, and flattened diurnal cortisol secretion in women with breast cancer.

“We are now finding that sleep disruption is much more common than we previously thought in cancer patients,” said lead author Oxana Palesh, PhD, assistant research professor, Departments of Radiation Oncology and Psychiatry at the University of Rochester Medical Center in New York. “Sleep appears to be as big of a problem as fatigue in patients, and it is as distressing.” Dr. Palesh believes that studying sleep disruption in cancer patients will help investigators unravel its causes, leading to preventions or treatments.

The study enrolled 99 women with a diagnosis of breast cancer. For 2 days, participants collected their saliva for 5 cortisol measurements. They also completed questionnaires and wore actimetry sensors to monitor sleep-wake cycles for 3 days. About 1 to 2 weeks after baseline measurements of cortisol, researchers obtained patients’ respiratory sinus arrhythmia (RSA) measurements prior to administering the Trier Social Stress Task (TSST) test, a standardized social and cognitive stress test. RSA was also measured during the TSST test.

Longer episodes of wakefulness during the night were associated with a flatter diurnal cortisol slope and diminished RSA levels during the TSST task. Investigators observed a significant relationship between higher baseline RSA scores and better sleep efficiency, lower levels of interrupted sleep, lower average length of wake episodes, and fewer self-reported hours of sleep during a typical night.

Higher RSA levels during TSST were linked significantly to superior sleep efficiency, fewer wake episodes, decreased incidence of waking after sleep onset (WASO), and shorter periods of wakefulness. For 4 of the 6 sleep parameters under study, the level of RSA best explained a patient’s sleep efficiency, WASO, and the mean number and average length of waking episodes, even after controlling for age, disease severity, type of treatment, and psychological variables, such as pain and stress.

“This is the first study that found a relationship between disrupted sleep and dysregulation of the parasympathetic nervous system,” says Dr. Palesh. “This opens up further areas of interest in the study of sleep disturbances and insomnia in cancer patients. In addition, if there is a lower vagal tone reason for the insomnia, patients can learn to regulate somewhat easily with well-known psychological and behavioral interventions.”

Dr. Palesh stresses the preliminary nature of the study’s findings but notes that most interventions for disruptions of the parasympathetic nervous system have little risk. Thus, clinicians may want to suggest yoga, slow breathing, and meditation and relaxation exercises for cancer patients who suffer sleep disturbances such as insomnia.

“This is a very timely paper because of the increased focus on quality of life issues for metastatic breast cancer patients,” says Sheryl Gabram-Mendola, MD, Professor of Surgery at Emory University and Winship Cancer Institute in Atlanta, Georgia. “This is a very well done study with in-depth data collection and reporting.”

Dr. Gabram-Mendola cautions that the study has some limitations. Participants were all women 45 years of age or older and, prior to accrual, 39% of patients were taking prescribed antidepressants and 19% were taking sleeping medication. She suggests, however, that the complex methodology and the fact that previous studies support its findings mitigate these concerns.

“It has been shown historically that decreased RSA [levels], the surrogate marker for parasympathetic tone used in this study, is associated with insomnia [and] variations in cortisol levels and potentially can impact…shorter survival,” said Dr. Gabram-Mendola. She notes that the “flattening of the diurnal cortisol pattern has also been linked to shorter survival” and says that while data from the study by Palesh et al support the results of prior studies, the findings are unique because they are specific to patients with metastatic breast cancer.

“This is the first very comprehensive analysis of the effect of hormonal and autonomic responses in individuals with sleep disturbances in metastatic breast cancer,” she says. “The take-home message for medical oncologists right now is that we are now a step closer to understanding the physiological mechanisms behind insomnia in patients with metastatic breast cancer and this will eventually lead us to figuring out the best ways to treat patients so they have an improved quality of life.”

Palesh O, et al. Vagal regulation, cortisol, and sleep disruption in women with metastatic breast cancer. J Clin Sleep Med. 2008;4(5):441-449.

Kurt Ullman is a freelance medical and health writer based out of Indianapolis.