Obesity, related comorbidities, and breast cancer outcomes in African Americans

描述(申请人提供)：与美国其他种族和民族相比，非裔美国人的乳腺癌(BRCA)预后较差可能是多因素的，包括肿瘤特征、社会经济因素和获得护理的机会较差。虽然有强有力的证据表明，肥胖和肥胖相关的并发症会增加欧洲血统女性(EAs)的BRCA和竞争性原因死亡率，但它在AAs中的预后作用尚不确定，潜在的调节机制尚未阐明。我们建议评估(1)身体肥胖(身体质量指数、体脂分布和身体成分)对接受BRCA治疗(包括减少和推迟化疗剂量)和结果(BRCA特有死亡率、竞争原因死亡率、全因死亡率、生活质量)的影响；(2)肥胖相关并发症(包括高血压和糖尿病)对BRCA治疗和结果的影响，以及对这些条件的最佳管理是否影响结果；以及(3)潜在的机制途径，包括免疫因子、维生素D、脂肪因子和胰岛素抵抗指标，它们可能介导肥胖和肥胖相关合并症的影响。使用祖先信息标记(AIMS)的基因类型获得的基因组祖先的估计将包括在所有分析中。我们建议进行一项具有成本效益的研究，该研究建立在正在进行的基于人群的再障女性BRCA病例对照研究基础上(P01，CA151135)。新泽西州癌症登记处(NJSCR)的快速病例确定用于识别新泽西州10个县的新诊断BRCA病例。我们建议将招募再生障碍性贫血病例的期限延长至2018年3月，将总数增加到约1,700例，其中约1,100例在确诊后18至24个月采集血样，约860例在确诊后30至36个月采集血样。我们建议建立一个AA BRCA幸存者队列，以评估护理、生活质量(QOL)和生存方面的差异，特别是与肥胖有关的差异。确诊后不久进行的基线家庭访谈收集了有关风险因素的信息，包括终生体重史。进行人体测量和身体成分测量，并采集唾液样本。获得并审查来自多个提供者的医疗记录。我们建议在治疗结束后约12个月和~24个月采集血液样本，以评估与肥胖相关的生物标志物，并进行年度主动和被动随访，并获取详细的医疗记录。积极的后续行动将包括采访以收集年度最新情况 关于人体测量、饮食和体力活动、病史，包括关于合并症及其处理的信息，以及生存因素(例如，生存质量、淋巴水肿、感觉到的压力和疲劳)。被动后续行动将包括与NJSCR的记录联系，以获得死者的生命状况、时间和死亡原因。这项研究的发现对于改善肥胖AA BRCA患者的临床管理，提高BRCA幸存者的生存和生活质量具有巨大的潜力。

DESCRIPTION (provided by applicant): Poorer breast cancer (BrCa) prognosis among African Americans (AAs) compared to other racial and ethnic groups in the United States is likely multifactorial, including tumor characteristics, socio-economic factors and poor access to care. While there is strong evidence that obesity and obesity-related comorbidities increase BrCa and competing cause mortality among women of European ancestry (EAs), its prognostic role among AAs is uncertain, and potential mediating mechanisms have not been elucidated. We propose to evaluate (1) the impact of body fatness (body mass index, body fat distribution, and body composition) on BrCa treatment received (including chemotherapy dose reduction and delay) and outcomes (BrCa-specific mortality, competing-cause mortality, all-cause mortality, quality-of-life); (2) the impact of obesity-related comorbidities which are more common among AAs, including hypertension and diabetes, in relation to BrCa treatment and outcomes, and whether optimal management of these conditions impact outcomes; and (3) potential mechanistic pathways, including immune factors, vitamin D, adipokines, and indicators of insulin resistance that potentially mediate the effects obesity and obesity-related comorbidities. Estimates of genomic ancestry, obtained using genotypes from Ancestry Informative Markers (AIMs) will be included in all analyses. We propose a cost-effective study that builds upon an ongoing population-based case-control study of BrCa in AA women (P01 CA151135). Rapid case ascertainment by the NJ State Cancer Registry (NJSCR) is used to identify newly diagnosed BrCa cases in ten counties in NJ. Here we propose to extend recruitment of AA cases up to March 2018, increasing the total number to ~1,700, with ~1,100 cases with blood samples collected 18 to 24 months after diagnosis and ~860 blood samples collected 30 to 36 months after diagnosis. We propose to establish a cohort of AA BrCa survivors to assess disparities in care, quality-of-life (QoL), and survival, particularly in relation to obesity. A baeline home interview conducted shortly after diagnosis collects information on risk factors, including lifetime weight history. Anthropometric and body composition measurements are taken and a saliva sample is collected. Medical records from multiple providers are obtained and reviewed. We propose to collect blood samples ~12 months and ~24 months after completion of treatment to evaluate obesity-related biomarkers, and to conduct annual active and passive follow-up and obtain detailed medical records. Active follow-up will involve interviews to collect annual updates on anthropometric measurements, diet and physical activity, medical history, including information on comorbidities and their management, as well as survivorship factors (e.g., QoL, lymphedema, perceived stress, and fatigue). Passive follow-up will include record linkage with the NJSCR to obtain vital status and time and causes of death for those who are deceased. Findings from this study have great potential to improve clinical management of obese AA BrCa patients to improve the survival and QoL of BrCa survivors.