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Many breast cancer survivors experience persistent physical symptoms of cancer and treatment that can decrease health-related quality of life (HRQOL). This prospective study investigated physical activity (PA), occurrence of physical symptoms, and HRQOL in a large, ethnically-diverse cohort of breast cancer survivors.Survivors (n = 545), on average 6 months post-diagnosis, were assessed in person or by mail at baseline (retrospective reports of pre-diagnosis PA), at 29 months post-diagnosis (post-diagnosis PA), and at 39 months post-diagnosis (pain, hormone symptoms, sexual interest/dysfunction, fatigue, physical subscales of HRQOL). Linear regression and analysis of covariance assessed the relationships between pre- and post-diagnosis PA and PA change after cancer with symptoms and HRQOL.Greater pre-diagnosis PA was associated with better physical functioning at 39 months (βs 1.1-2.3; all p < 0.01) but was generally unrelated to symptoms. Greater post-diagnosis sports/recreational PA was related to less fatigue and better physical functioning (βs -0.146, 2.21; both p < 0.01). Increased PA after cancer was related to less fatigue and pain and better physical functioning (all p < 0.01). Significant positive associations were found for moderate to vigorous and vigorous sports/recreation PA, not household activity. Results were similar for Hispanic and non-Hispanic White women.Increased PA, especially after cancer, was consistently related to better physical functioning and to reduced fatigue and bodily pain, underscoring the need for PA promotion among survivors.Survivors may be able to decrease fatigue and bodily pain and be better able to pursue daily activities through increasing recreational PA after cancer.