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Objectives. This study compares the effects of an integrated yoga program with brief supportive therapy in breast cancer outpatients undergoing adjuvant radiotherapy at a cancer center. Methods. Eighty-eight stage II and III breast cancer outpatients are randomly assigned to receive yoga (n = 44) or brief supportive therapy (n = 44) prior to radiotherapy treatment. Assessments include diurnal salivary cortisol levels 3 days before and after radiotherapy and self-ratings of anxiety, depression, and stress collected before and after 6 weeks of radiotherapy. Results. Analysis of covariance reveals significant decreases in anxiety (P < .001), depression (P = .002), perceived stress (P < .001), 6 a.m. salivary cortisol (P = .009), and pooled mean cortisol (P = .03) in the yoga group compared with controls. There is a significant positive correlation between morning salivary cortisol level and anxiety and depression. Conclusion. Yoga might have a role in managing self-reported psychological distress and modulating circadian patterns of stress hormones in early breast cancer patients undergoing adjuvant radiotherapy.