PHYSICAL ACTIVITY AND RISK OF BREAST CANCER

乳腺癌是美国女性最常见的癌症，也是导致癌症死亡的第二大原因。不幸的是，这种疾病的既定危险因素通常是不可改变的。体力活动被认为可以降低患乳腺癌的风险，几种看似合理的生物学机制确实支持了这一假设。然而，流行病学研究报告了高度不一致的结果。因为病例对照研究比队列研究更一致地观察到反向关联，病例对照研究中的回忆偏差可能是造成差异的部分原因。还没有研究评估这种可能的偏见的程度。此外，如果体力活动通过内源性激素机制影响乳腺癌风险，它应该与ER+/PR+的乳腺癌有更强的相关性。这个问题以前从未被探讨过。最后，目前还不清楚是否需要终生体育锻炼来降低乳腺癌风险；过去只有一项研究对此进行了检验。为了解决这些问题，我们建议使用已经从女性健康研究(WHS)中年龄大于或等于45岁的39,876名女性收集的数据来检查前瞻性确定的中年体力活动与所有乳腺癌(n=412)和仅ER+/PR+乳腺癌(n=222)风险的相关性。此外，我们建议对这412名患有乳腺癌的女性和824名对照进行病例对照研究，匹配年龄和随机进入WHS的日期的病例，现在将追溯收集相同的体力活动信息。这将允许评估病例对照研究中关于体力活动与乳腺癌关系的任何可能的偏倚。此外，病例对照研究将收集12岁以来的体力活动信息，使我们能够评估终生体力活动。这项建议，以相对较少的成本，将帮助我们更好地了解体力活动与乳腺癌的关系。

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among US women. Unfortunately, established risk factors for this disease generally are non-modifiable. Physical activity has been proposed to decrease breast cancer risk and several plausible biologic mechanisms do support this hypothesis. However, epidemiologic studies have reported highly inconsistent findings. Because case-control studies have more consistently observed inverse associations than have cohort studies, recall bias in case-control studies may account, partly, for the discrepancies. No study has assessed the extent of this possible bias. Further, if physical activity were to influence breast cancer risk via an endogenous hormonal mechanism, it should be more strongly related to breast cancers that are ER+/PR+. This question has not previously been explored. Finally, it is unclear whether lifetime physical activity is needed to decrease breast cancer risk; only one past study has examined this. To address these issues, we propose using already collected data from 39,876 women, aged greater than or equal to 45 years, in the Women's Health Study (WHS) to examine the associations of physical activity in middle-age, ascertained prospectively, with risk of all breast cancer (n=412) and of only ER+/PR+ breast cancers (n=222). Further, we propose to conduct a case-control study of these 412 women with breast cancer and 824 controls, matched to cases on age and date of randomization into the WHS, where the same information on physical activity now will be collected retrospectively. This will allow evaluation of any possible bias from case-control studies regarding the physical activity-breast cancer relation. Additionally, the case-control study will gather information on physical activity since age 12 years, allowing us to assess lifetime physical activity. This proposal, at relatively little cost, will help us better understand the physical activity-breast cancer relation.