Abstract Purpose: TomoBreast compared normofractionated conventional radiotherapy (CR) with hypofractionated tomotherapy (TT), on the hypothesis that normal-tissue sparing by tomotherapy should reduce lung-heart toxicity. Quality of life (QOL) outcomes at 8-12 years are presented herein. Materials-Methods: The trial enrolled 123 women in 2007-2011, 64 were randomized to CR, 59 to TT. CR delivered 50 Gy in 25 fractions/5 weeks to the breast/chest wall and regional nodes if node-positive, 16 Gy/8 fractions/1.6 weeks sequential-boost in patients who underwent lumpectomy. TT delivered 42 Gy/15 fractions/3 weeks to the breast/chest wall and regional nodes if node-positive, concurrently with chemotherapy by institution's practice, 51 Gy simultaneous-integrated-boost in patients with lumpectomy. QOL assessments used the EORTC questionnaires QLQ-C30 and QLQ-BR23. Intent-to-treat analyses used the linear mixed-effect model (LMM), and survival analysis applied to time to >10% deterioration (TTD) in QOL-measures. A cardiorespiratory composite TTD event was defined as deterioration in any of the dyspnea, fatigue, physical functioning, or pain measures. Results: On survival and tumor control, there were no differences in overall and disease-free survival. On QOL analysis by LMM, TT in late >2 years period was associated with poorer nausea-scores (modeled deterioration 21.2%, P<0.001), better cognitive functioning (15.7%, P<0.001), better freedom from dyspnea (9.4%, P=0.027), and better freedom from financial stress (13.3%, P<0.001) (Table 1, P-values * ≤.05; ** ≤.01; *** ≤.001). By TTD, the composite outcome showed reduced risk of cardiorespiratory deterioration; the estimated 10-years risk of deterioration was 29.8% in the CR arm versus 13.8% in the TT arm, P=0.033. Conclusion: The long term result shows significantly better cardiorespiratory and other QOL scores in favor of hypofractionation with tomotherapy. Clinical trials to further enhance lung-heart outcome in breast cancer radiotherapy should be considered. Linear mixed model by Time and Tomotherapy. Coef: %change from baselineEarly (≤2 years) assessmentLate (>2 years) assessmentTime Early effect coef/yearP- Tomotherapy Early effectP- Time Late effect coef/yearP- Tomotherapy Late effectP- Global health status11.3*-7.4*-0.6-4.7C30 summary5.8**-1.2-0.62.2Physical functioning5.30.3-0.5-1.0Role functioning25.0***-4.5-1.32.1Emotional functioning2.20.7-0.75.2Cognitive functioning3.63.1-1.5*15.7***Social functioning13.4**-2.1-1.0-8.4Fatigue free13.7**-1.6-0.62.3Appetence12.2**-0.70.52.1Nausea vomiting free9.3-12.1*-0.6-21.2***Constipation free-0.50.5-1.07.3Diarhea free3.1-3.3-0.7-3.6Pain free10.8-4.7-0.1-2.3Dyspnea free4.90.8-0.89.4*Sleep loss free3.2-2.80.3-1.4Financial stress free1.03.1-0.213.3***Good body image24.3**1.7-0.99.5Sexual functioning13.10.5-3.3-3.3Sexual enjoyment-1.6-4.31.8-2.1Future worry-free18.0**-5.6-1.0-13.3Systemic symptom free3.30.30.14.3Breast symptom free12.1**-0.50.65.2Arm symptom free-0.80.2-0.53.8Hair loss free23.40.5-0.3-20.6 Citation Format: Hilde Van Parijs, Vincent Vinh-Hung, Christel Fontaine, Guy A Storme, Nele Adriaenssens, Shane Hanon, Marian Vanhoeij, Maryam B Lustberg, Nicole Williams, Dung M Nguyen, Nam P Nguyen, Claire Verschraegen, Mark De Ridder. Quality of life in survivors of stage I-II breast cancer, 10 years outcome of a randomized clinical trial comparing post-operative hypofractionation with Tomotherapy versus conventional radiation treatment (TomoBreast) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-01.