There is a paucity of research investigating the potential of exercise to mitigate cancer-related fatigue (CRF) during radiotherapy for the treatment of breast cancer. Aims: To examine the efficacy of a home-based exercise program involving resistance and aerobic exercise to ameliorate CRF in breast cancer patients during and after radiotherapy. Methods: Seventy-seven breast cancer patients scheduled to receive radical radiotherapy were randomised into exercise (n=35) or usual care (n=42) groups subject to maintaining balance for prior chemotherapy (yes/no), number of fractions (<25≥) and age (≤55>). The exercise group participated in a 12-week home-based exercise program involving resistance and aerobic exercise prescription supplemented by a 1-hour face-to-face consultation, four 30 minute telephone consultations, a theoretically-based exercise manual and exercise equipment (Gymstick, pedometer). Assessments were conducted prior to initiating radiotherapy (week 0), post-radiotherapy (week 6 and 12); data collection is ongoing for 6 and 12 months post-radiotherapy. CRF was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire. Self-reported physical activity level (Godin Leisure-Time Exercise Questionnaire) and quality of life (SF-36 Health Survey) were also determined. Results: Preliminary analyses are reported here but the accrual target (n=100) will be met and final data presented at the conference. No between-group differences were observed for change in fatigue at post- or 6 weeks post-treatment (p=0.394 and 0.172 respectively). Change in aerobic exercise levels did not differ between groups but change in resistance exercise level was greater in the exercise group at post- (39 minutes, CI 22-56, p<0.001) and 6-weeks post-radiotherapy (41 minutes, CI 16-66, p=0.002). Change in social functioning differed between groups at post-radiotherapy (3.9, CI 0.4-7.5, p=0.030), no differences existed across other quality of life domains. Conclusions: A home-based exercise program did not improve fatigue but increased resistance exercise participation and improved social functioning in breast cancer patients receiving radiotherapy.