“The median survival difference was about 2 years, so this is not a trivial difference in overall survival,” he said, stressing that the finding is based on more chronic and severe depression.
Other studies have demonstrated relationships between circadian rhythm disruption and cancer survival. In one such study involving patients with metastatic colorectal cancer, circadian rhythm/rest activity cycle (more activity during the day, more rest at night) was associated with better quality of life and predicted survival.
“This has been shown now in several cancers, and it’s clear that a combination of higher activity and better sleep predict longer survival with different kinds of cancers,” Dr. Spiegel said, explaining that a hallmark of a healthy hypothalamic-pituitary-adrenal axis is good diurnal variation of cortisol with high levels in the morning and declining levels throughout the day.
Women with metastatic breast cancer and poorer survival tended to have flat or increasing levels of cortisol throughout the day, he said, adding that the same was true in a study of patients with lung cancer, and that there is evidence that those among them with flatter, more abnormal cortisol patterns throughout the day also have shorter survival.
Animal studies suggest that cortisol might directly suppress the activity of tumor suppressor genes, he explained, noting that there is also increasing evidence of autonomic dysregulation effects on inflammatory processes associated with tumor growth.
“Some basic research on this in animal models shows that if you block adrenergic arousal, you can block the growth of blood vessels from tumors. This has led some people to look at the use of antiadrenergic drugs like the beta-blocker propranolol, and it turned out – to everyone’s surprise – that breast cancer patients who happened to be on beta-blockers for hypertension actually lived longer than those who didn’t,” he said.
This adds to the growing evidence that dysregulation in the sympathetic and parasympathetic systems have effects on survival, he said.
A look at another factor related to sleep disruption – bedtime misalignment – showed that patients who adhere to their preferred sleep pattern, and who are therefore sleeping better, had a difference in disease-free interval; those whose bedtime was misaligned had a shorter time between diagnosis and disease recurrence (Chronobiol Int. 2014 Mar 31[2]214-21).
“Disease-free interval is a very strong predictor of ultimate overall survival, so there seems to be another relationship here between circadian disruption and disease progression in breast cancer,” Dr. Spiegel said.
Taken together, these findings demonstrate a strong association between vagal activity and survival in patients with metastatic or recurrent breast cancer, extending the known predictive window of HF-HRV beyond palliative care to cancer, Dr. Spiegel said.
“Vagal activity can be altered through behavioral, pharmacological, and surgical interventions and thus may be a promising target for increasing survival in patients with metastatic cancer,” he said.
Dr. Spiegel’s studies were funded by the National Cancer Institute and the National Institute on Aging.