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BACKGROUND: Studies have shown that distress and accompanying neuroendocrine stress responses as important predictor of survival in advanced breast cancer patients. Some psychotherapeutic intervention studies have shown have modulation of neuroendocrine-immune responses in advanced breast cancer patients. In this study, we evaluate the effects of yoga on perceived stress, sleep, diurnal cortisol, and natural killer (NK) cell counts in patients with metastatic cancer.METHODS: In this study, 91 patients with metastatic breast cancer who satisfied selection criteria and consented to participate were recruited and randomized to receive "integrated yoga based stress reduction program" (n = 45) or standard "education and supportive therapy sessions" (n = 46) over a 3 month period. Psychometric assessments for sleep quality were done before and after intervention. Blood draws for NK cell counts were collected before and after the intervention. Saliva samples were collected for three consecutive days before and after intervention. Data were analyzed using the analysis of covariance on postmeasures using respective baseline measure as a covariate. RESULTS: There was a significant decrease in scales of symptom distress (P < 0.001), sleep parameters (P = 0.02), and improvement in quality of sleep (P = 0.001) and Insomnia Rating Scale sleep score (P = 0.001) following intervention. There was a decrease in morning waking cortisol in yoga group (P = 0.003) alone following intervention. There was a significant improvement in NK cell percent (P = 0.03) following intervention in yoga group compared to control group. CONCLUSION: The results suggest modulation of neuroendocrine responses and improvement in sleep in patients with advanced breast cancer following yoga intervention.