BACKGROUND The long time from exposure to potentially harmful chemicals until breast cancer occurrence poses challenges for designing etiologic studies and for implementing successful prevention programs. Growing evidence from animal and human studies indicates that distinct time periods of heightened susceptibility to endocrine disruptors exist throughout the life course. The influence of environmental chemicals on breast cancer risk may be greater during several windows of susceptibility (WOS) in a woman's life, including prenatal development, puberty, pregnancy, and the menopausal transition. These time windows are considered as specific periods of susceptibility for breast cancer because significant structural and functional changes occur in the mammary gland, as well as alterations in the mammary micro-environment and hormone signaling that may influence risk. Breast cancer research focused on these breast cancer WOS will accelerate understanding of disease etiology and prevention. MAIN TEXT Despite the plausible heightened mechanistic influences of environmental chemicals on breast cancer risk during time periods of change in the mammary gland's structure and function, most human studies of environmental chemicals are not focused on specific WOS. This article reviews studies conducted over the past few decades that have specifically addressed the effect of environmental chemicals and metals on breast cancer risk during at least one of these WOS. In addition to summarizing the broader evidence-base specific to WOS, we include discussion of the NIH-funded Breast Cancer and the Environment Research Program (BCERP) which included population-based and basic science research focused on specific WOS to evaluate associations between breast cancer risk and particular classes of endocrine-disrupting chemicals-including polycyclic aromatic hydrocarbons, perfluorinated compounds, polybrominated diphenyl ethers, and phenols-and metals. We outline ways in which ongoing transdisciplinary BCERP projects incorporate animal research and human epidemiologic studies in close partnership with community organizations and communication scientists to identify research priorities and effectively translate evidence-based findings to the public and policy makers. CONCLUSIONS An integrative model of breast cancer research is needed to determine the impact and mechanisms of action of endocrine disruptors at different WOS. By focusing on environmental chemical exposure during specific WOS, scientists and their community partners may identify when prevention efforts are likely to be most effective.

中文翻译：

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乳腺癌易感性窗口期间的环境暴露：预防研究框架。

背景从接触潜在有害化学品到发生乳腺癌的漫长时间对设计病因学研究和实施成功的预防计划提出了挑战。来自动物和人类研究的越来越多的证据表明，在整个生命过程中存在对内分泌干扰物高度易感性的不同时期。在女性生命中的几个易感窗口 (WOS) 期间，包括产前发育、青春期、怀孕和绝经过渡期，环境化学物质对乳腺癌风险的影响可能更大。这些时间窗被认为是乳腺癌易感的特定时期，因为乳腺发生了显着的结构和功能变化，以及可能影响风险的乳腺微环境和激素信号的改变。专注于这些乳腺癌 WOS 的乳腺癌研究将加速对疾病病因学和预防的理解。正文 尽管在乳腺结构和功能发生变化的时间段内，环境化学物质对乳腺癌风险的机械影响可能会增强，但大多数环境化学物质的人类研究并不关注特定的 WOS。本文回顾了过去几十年进行的研究，这些研究至少在其中一个 WOS 期间专门解决了环境化学物质和金属对乳腺癌风险的影响。除了总结特定于 WOS 的更广泛的证据基础之外，我们包括对 NIH 资助的乳腺癌和环境研究计划 (BCERP) 的讨论，其中包括以特定 WOS 为重点的基于人群和基础科学研究，以评估乳腺癌风险与特定类别的内分泌干扰化学物质（包括多环芳烃）之间的关联碳氢化合物、全氟化合物、多溴二苯醚、酚类和金属。我们概述了正在进行的跨学科 BCERP 项目如何与社区组织和传播科学家密切合作，将动物研究和人类流行病学研究结合起来，以确定研究重点，并将基于证据的发现有效地转化为公众和政策制定者。结论 需要一个乳腺癌研究的综合模型来确定内分泌干扰物在不同 WOS 下的影响和作用机制。通过关注特定 WOS 期间的环境化学物质暴露，科学家及其社区合作伙伴可以确定何时预防工作可能最有效。