Physical activity, risk of death and recurrence in breast cancer survivors: A systematic review and meta-analysis of epidemiological studies

UNLABELLED: Strong evidence exists supporting the effect of lack of physical activity on the risk of developing breast cancer. However, studies examining the effects of physical activity on breast cancer outcomes, including survival and prognosis have been inconclusive. Therefore, the aim of the current study was to provide a systematic review and meta-analysis of studies investigating the association between physical activity and breast cancer recurrence and death. METHODS: PubMed, EMBASE, and CENTRAL databases were searched up to 18 October 2014. Reference lists of retrieved articles and relevant previous reviews were also searched. Observational studies that reported risk estimates for all-cause and/or breast cancer-related death and/or breast cancer recurrences by levels of physical activity, were included in the review. Random effects models were used to calculate pooled hazard ratios (HR) and 95% confidence intervals (CI) and to incorporate variation between studies. The Newcastle-Ottawa scale was used to critically appraise the risk of bias across studies. RESULTS: Twenty-two prospective cohort studies were eligible in this meta-analysis. During average follow-up periods ranging from 4.3 to 12.7 years there were 123 574 participants, 6898 all-cause deaths and 5462 breast cancer outcomes (i.e. breast cancer-related deaths or recurrences). The average Newcastle-Ottawa score was six stars (range 4-8). Compared to those who reported low/no lifetime recreational pre-diagnosis physical activity, participants who reported high lifetime recreational pre-diagnosis physical activity levels had a significantly lower risk of all-cause (HR = 0.82, 95% CI 0.70-0.96, p < 0.05) and breast cancer-related death (HR = 0.73, 95% CI 0.54-0.98, p < 0.05). Significant risk reductions for all-cause and breast cancer-related death was also demonstrated for more recent pre-diagnosis recreational physical activity (HR = 0.73, 95% CI 0.65-0.82, p < 0.001; and HR = 0.84, 95% CI 0.73-0.97, p < 0.05, respectively), post-diagnosis physical activity (HR = 0.52, 95% CI 0.43-0.64, p < 0.01; and HR = 0.59, 95% CI 0.45-0.78, p < 0.05, respectively) and meeting recommended physical activity guidelines (i.e. ≥ 8 MET-h/wk) post-diagnosis (HR = 0.54, 95% CI 0.38-0.76, p < 0.01; and HR = 0.67, 95% CI 0.50-0.90, p < 0.01, respectively). However, there was evidence of heterogeneity across lifetime recreational pre- and post-diagnosis physical activity analyses. Both pre-diagnosis (lifetime and more recent combined) and post-diagnosis physical activity were also associated with reduced risk of breast cancer events (breast cancer progression, new primaries and recurrence combined) (HR = 0.72 95% CI 0.56-0.91, p < 0.01; and HR = 0.79, 95% CI 0.63-0.98, p < 0.05, respectively). CONCLUSION: There is an inverse relationship between physical activity and all-cause, breast cancer-related death and breast cancer events. The current meta-analysis supports the notion that appropriate physical activity may be an important intervention for reducing death and breast cancer events among breast cancer survivors.