Purpose Inflammation is linked to tumor proliferation and metastasis in cancers. Yoga therapy has been claimed to down regulate inflammation leading to positive impact on patient’s physical and psychosocial health. We studied the long term effect of yogic intervention on breast cancer patients undergoing chemotherapy and radiotherapy. Methodology 96 stage II/III breast cancer patients receiving radiotherapy and/or chemotherapy were randomized into group-I (control) undergoing chemotherapy and radiation therapy and group-II (intervention) having additional yogic practice. The yoga group performed yoga for 5days/week for 48 weeks with well structured yogic practices. Cytokines were assayed at 0th, 16th, 32nd, and 48th weeks using Human Cytokine Magnetic 10-Plex Panel. The cytokines studied are IL-1β, IL-2, IL-6, IL-8, IFN-γ, TNF-α, GM-CSF, IL-4, IL-5, and IL-10. Results Quality of life improved significantly in patients practicing yoga therapy treatment arm in addition to symptomatic improvement. The level of IL-1β, IL-10, TNF-α and IFN-γ (pg/ml) showed the significant difference between the group-I and group-II (P<0.001) showing down-regulation of inflammatory markers. The most significant difference was observed between 1st and 48 weeks. There was no difference in the level of IL-2, IL-4, IL-5, IL-6, IL-8, and GM-CSF. Conclusions Our current findings showed that long-term yogic intervention promotes a strong immune response in breast cancer patients by lowering inflammatory cytokines. It improves functional status leading to overall improvement of quality of life.