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Many epidemiologic studies have found an association between physical activity and breast cancer risk, although this has not been a consistent finding.Studies were identified through a systematic review of literature available on PubMed through February 2006. We included all cohort and case–control studies that assessed total or leisure time activities in relation to occurrence or mortality of breast cancer. The fully adjusted risk estimates and 95% confidence intervals for the highest versus lowest level of activity were documented for each study as well as evidence for a dose–response relationship. Methodologic quality was also assessed. Due to statistical and methodologic heterogeneity among studies, we did not carry out statistical pooling. To draw conclusions, we performed a best-evidence synthesis taking study quality into account.Nineteen cohort studies and 29 case–control studies were evaluated. There was strong evidence for an inverse association between physical activity and postmenopausal breast cancer with risk reductions ranging from 20% to 80%. For premenopausal breast cancer, however, the evidence was much weaker. For pre- and postmenopausal breast cancer combined, physical activity was associated with a modest (15–20%) decreased risk. Evidence for a dose–response relationship was observed in approximately half of the higher-quality studies that reported a decreased risk. A trend analysis indicated a 6% (95% confidence interval = 3% to 8%) decrease in breast cancer risk for each additional hour of physical activity per week assuming that the level of activity would be sustained.There is evidence for an inverse association between physical activity and breast cancer risk. The evidence is stronger for postmenopausal breast cancer than for premenopausal breast cancer.