Wang Ziyu, Albers Frances Em, Wang Sabrina E, English Dallas R, Lynch Brigid M
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia; Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia.
Cancer Epidemiol. 2024 Apr;89:102544. doi: 10.1016/j.canep.2024.102544. Epub 2024 Feb 14.
Pre-diagnostic physical activity is reported to improve survival for women with breast cancer. However, studies of pre-diagnostic exposures and cancer survival are susceptible to bias, made clear when applying a target trial framework. We investigated the impact of selection bias, immortal time bias, confounding and bias due to inappropriate adjustment for post-exposure variables in a systematic review and meta-analysis of pre-diagnostic physical activity and survival after breast cancer.
Medline, Embase and Emcare were searched from inception to November 2021 for studies examining pre-diagnostic physical activity and overall or breast cancer-specific survival for women with breast cancer. Random-effects meta-analysis was used to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs) comparing highest versus lowest pre-diagnostic physical activity. Subgroup meta-analyses were used to compare HRs of studies with and without different biases. ROBINS-E was used to assess risk of bias.
We included 22 studies. Women with highest versus lowest pre-diagnostic physical activity had higher overall and breast cancer-specific survival across most analyses. The overall risk of bias was high. We observed marked differences in estimated HRs between studies that did and did not adjust for post-exposure variables or have immortal time bias. All studies were at risk of selection bias due to participants becoming eligible for study when they have survived to post-exposure events (e.g., breast cancer diagnosis). Insufficient studies were available to investigate confounding.
Biases can substantially change effect estimates. Due to misalignment of treatment assignment (before diagnosis), eligibility (survival to post-exposure events) and start of follow-up, bias is difficult to avoid. It is difficult to lend a causal interpretation to effect estimates from studies of pre-diagnostic physical activity and survival after cancer. Biased effect estimates that are difficult to interpret may be less useful for clinical or public health policy applications.
据报道，诊断前的身体活动可提高乳腺癌女性的生存率。然而，对诊断前暴露与癌症生存的研究容易产生偏倚，在应用目标试验框架时这一点很明显。我们在一项关于诊断前身体活动与乳腺癌后生存的系统评价和荟萃分析中，研究了选择偏倚、不朽时间偏倚、混杂因素以及因对暴露后变量进行不适当调整而导致的偏倚的影响。
检索Medline、Embase和Emcare数据库，从建库至2021年11月，查找研究诊断前身体活动与乳腺癌女性总体生存或乳腺癌特异性生存的研究。采用随机效应荟萃分析来估计比较诊断前身体活动最高与最低水平的合并风险比（HR）和95%置信区间（CI）。亚组荟萃分析用于比较有无不同偏倚的研究的HR。使用ROBINS-E评估偏倚风险。
我们纳入了22项研究。在大多数分析中，诊断前身体活动最高与最低的女性总体生存和乳腺癌特异性生存更高。总体偏倚风险较高。我们观察到，在未对暴露后变量进行调整或存在不朽时间偏倚的研究与进行了调整的研究之间，估计的HR存在显著差异。由于参与者在经历暴露后事件（如乳腺癌诊断）后存活才符合研究条件，所有研究都存在选择偏倚风险。没有足够的研究可用于调查混杂因素。
偏倚可显著改变效应估计值。由于治疗分配（诊断前）、入选资格（存活至暴露后事件）和随访开始之间的不一致，偏倚难以避免。很难对诊断前身体活动与癌症后生存的研究中的效应估计值进行因果解释。难以解释的有偏效应估计值可能对临床或公共卫生政策应用用处较小。
