The Role of 27-hydroxycholesterol in Breast Cancer: A Population-Based Multiethnic Study

摘要 本申请是根据特别关注通知（NOSI）（编号为NOT-CA-20-037）提交的。 乳腺癌的中位生存率稳步提高，现在超过90%的患者将生存至少5年。 在最初的诊断后几年。随着老年乳腺癌幸存者人数的不断增加，人们的注意力已经 现在转向最初乳腺癌后新的合并症、症状和并发症的发生 诊断，以及老龄化的综合影响和乳腺癌的后果及其治疗在老年妇女。 多病性（MM）定义为个体发生两种或多种慢性疾病（或疾病）， 作为多系统故障以及随着时间的推移复原力和功能储备逐渐丧失的一个替代指标， 年龄本补充申请旨在研究MM累积与以下风险之间的关系： 使用长期的多种族队列（MEC）在乳腺癌发病妇女中选择衰老表型 study.具体来说，我们将研究MM模式（MMP; MM的数量、类型、簇， MM的持续时间和治疗）以及与衰老相关的三个公认的身体功能指标：活动 日常生活活动（ADL），工具性日常生活活动（IADL）和移动性。本补充提案将基于 母公司MEC R 01研究“27-羟基胆固醇在乳腺癌中的作用：一项基于人群的 多种族研究”（MPI：L。Loo/I. Cheng）通过研究乳腺癌生存率与MMP的关系，以及特定的 MMP簇，如心血管疾病和血脂异常，直接相关的27- 羟基胆固醇途径 我们提出以下目标：目标1：描述MMP（数量、类型和 MM的集群，MM的持续时间和治疗），在MEC中9121例乳腺癌患者中。 我们将使用基线和随访问卷以及医疗保险索赔数据评估MMP， 癌症病例以检查癌症诊断前和癌症诊断后MMP与人口统计学因素（年龄， 种族/民族，婚姻状况，教育），生活方式和健康行为（体重，饮食模式，体育活动， 吸烟）以及社会和背景因素（邻里社会经济地位，种族飞地）。我们将 评估MMP随时间推移与所有女性和种族/民族乳腺癌发病率的关系。 目标二。在3358名女性中调查与MMP相关的身体功能残疾的风险， 乳腺癌的发病率我们将使用三种身体功能残疾的老化指标（ADL，IADL和 在后续调查问卷中进行评估。我们将评估MMP病史随时间的变化与 结果ADL，IADL，和流动性分别以及乳腺癌病例中的组合指数。目标3： 评估MMP和身体功能残疾对3358名女性总死亡率的影响， 乳腺癌的发病率在乳腺癌病例的前瞻性分析中，我们将调查是否 乳腺癌存活率与（a）诊断前和诊断后MMP;（B）身体功能障碍（ADL， IADL和活动性）单独和作为组合指数;以及（c）诊断前和诊断后MMP和身体功能 联合模型中的残疾

Abstract This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-20-037. The median survival of breast cancer has improved steadily so that over 90% of patients will now survive at least 5 years after their initial diagnosis. As the number of older breast cancer survivors continues to increase, attention has now shifted to the occurrence of new comorbidities, symptoms, and complications after the initial breast cancer diagnosis, and the combined impact of aging and the consequences of breast cancer and its treatment in older women. Multimorbidities (MM) defined as the occurrence of two or more chronic conditions (or morbidities) in an individual may be a proxy measure of multisystem failures and progressive loss of resilience and functional reserve with increasing age. This supplement application aims to investigate the relationship between the accumulation of MM and risk of select aging phenotypes among women with incident breast cancer using the long-standing Multiethnic Cohort (MEC) study. Specifically, we will examine the relationships between MM patterns (MMP; number, type, clusters of MM, duration of MM and treatment) and three well-established metrics of physical function associated with aging: activities of daily living (ADL), instrumental activities of daily living (IADL), and mobility. This supplement proposal will build upon the parent MEC R01 study “The Role of 27-hydroxycholesterol in Breast Cancer: A Population-Based Multiethnic Study” (MPI: L. Loo/I. Cheng) by studying breast cancer survivorship in relation to MMP, as well as specific clusters of MMP such as cardiovascular disease and dyslipidemia that are directly relevant to the 27- hydroxycholesterol pathway. We propose the following aims: Aim 1: To characterize the relationship of MMP (number, type, and clusters of MM, duration of MM and treatment) among 9121 women with incident breast cancer in the MEC. We will assess MMP using baseline and follow-up questionnaires and Medicare claims data among incident breast cancer cases to examine the associations of pre- and post- cancer diagnosis MMP with demographic factors (age, race/ethnicity, marital status, education), lifestyle and health behaviors (body weight, dietary patterns, physical activity, smoking) as well as social and contextual factors (neighborhood socioeconomic status, ethnic enclaves). We will assess the association of MMP over time with breast cancer incidence among all women and by racial/ethnic groups. Aim 2. To investigate the risk of physical function disabilities associated with MMP among 3358 women with incident breast cancer in the MEC. We will use three aging metrics of physical function disabilities (ADL, IADL, and mobility) assessed in follow-up questionnaire. We will evaluate the associations of a history of MMP over time with the outcomes ADL, IADL, and mobility separately as well as a combined index among breast cancer cases. Aim 3: To assess the impact of MMP and physical function disabilities on overall mortality among 3358 women with incident breast cancer in the MEC. In a prospective analysis of breast cancer cases, we will investigate whether breast cancer survival is associated with (a) pre- and post-diagnostic MMP; (b) physical function disabilities (ADL, IADL, and mobility) separately and as a combined index; and (c) pre- and post-diagnostic MMP and physical function disabilities in a joint model