Disparities in breast cancer risk by HIV status: An exploration of sociodemographic differences between women with and without HIV and potential viral mechanisms for breast cancer risk reduction

7.项目摘要/摘要 具体目标：拟议的研究有三个目标：1)描述艾滋病的累积发病率 2000-2017年接受抗逆转录病毒治疗的女性中的乳腺癌，按日历时间分层(2000-2005， 2006-2011年、2012-2017年)；1)估计接受抗逆转录病毒治疗的妇女患乳腺癌的风险 比较2007-2017年间高病毒载量和低病毒载量妇女的社会人口学因素；2)估计 绝经前和围绝经期感染HIV和未感染HIV以及感染HIV病毒的妇女雌激素(雌二醇)的差异 艾滋病病毒携带者(WHIV)的载量；3)确定循环中的雌二醇和 携带和不携带艾滋病毒的妇女患绝经后乳腺癌的风险。 意义：这三个目标将为乳腺癌的病因学以及艾滋病毒 可能在癌症的发展中起作用。如果有和没有的女性之间的社会人口统计学差异 艾滋病毒大大降低了WHIV患乳腺癌的风险，进而降低了乳腺癌的发病率 WHIV可能会上升，这对妇女艾滋病毒的临床管理具有重要影响。如果HIV病毒 感染似乎有助于降低风险，这项研究将产生关于 艾滋病毒和免疫功能在乳腺癌病因和潜在的癌症治疗新机制中的作用。 方法：数据来源包括两项大型的前瞻性队列研究，这些研究获取了经过验证的癌症诊断 以及相关的协变量。对于目标1a和1b，我们将利用北美艾滋病队列协作 研究和设计(NA-ACCORD)表征乳腺癌及其相关疾病的累积发病率 与WHIV病毒载量的相关性。目标2和目标3的研究人群将是妇女机构间 艾滋病毒研究(WIHS)。对于目标2，绝经前和围绝经期妇女预先存在雌二醇测量将 用来评估艾滋病毒状况和雌二醇之间的关系，以及在WHIV之间的关系 HIV病毒载量和雌二醇之间的关系。目标3：绝经后妇女嵌套病例对照研究 在WIHS中，将进行评估艾滋病毒和雌二醇对乳腺癌风险的关系。 奖学金培训：Sally Coburn是约翰霍普金斯大学流行病学系的博士生 彭博公共卫生学院。拟议的研究包括她的论文研究，这将是 将与选定的赞助商和提供不同内容专业知识的三名导师合作进行。 这项研究嵌套在一个更大的、全面的培训计划中，包括课程和 教学和专业发展的机会。

7. PROJECT SUMMARY/ABSTRACT Specific aims: There are three aims for the proposed research: 1a) To describe the cumulative incidence of breast cancer in women with antiretroviral treated HIV in 2000-2017, stratified by calendar time (2000-2005, 2006-2011, 2012-2017); 1b) To estimate the risk of breast cancer in women with antiretroviral treated HIV comparing women with high versus low viral load in 2007-2017 by sociodemographic factors; 2) To estimate differences in estrogen (estradiol) in pre and perimenopausal women with versus without HIV, and by HIV viral load among women with HIV (WHIV); 3) To determine the association between circulating estradiol and the risk of postmenopausal breast cancer in women with and without HIV. Significance: These three aims will provide novel evidence on the etiology of breast cancer, and whether HIV could play a role in cancer development. If sociodemographic differences between women with and without HIV contribute substantially to the reduced risk of breast cancer in WHIV, then the incidence of breast cancer will likely rise in WHIV, which has important implications for the clinical management of HIV in women. If HIV infection appears to contribute to this reduced risk, this research will generate hypotheses regarding the role of HIV and immune function in breast cancer etiology and potential novel mechanisms for cancer therapy. Approach: Data sources include two large, prospective cohort studies, capturing validated cancer diagnoses and relevant covariates. For Aim 1a and 1b, we will use the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) to characterize the cumulative incidence of breast cancer and its association with viral load in WHIV. The study population for Aims 2 and 3 will be the Women’s Interagency HIV Study (WIHS). For Aim 2, pre and perimenopausal women with pre-existing estradiol measurements will be utilized to assess the relationship between HIV status and estradiol, and among WHIV, the relationship between HIV viral load and estradiol. For Aim 3, a nested case-control study among postmenopausal women in the WIHS will be conducted to evaluate the relationship between HIV and estradiol on breast cancer risk. Fellowship training: Sally Coburn is a PhD student in the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health. The proposed research encompasses her dissertation research, which will be conducted in collaboration with the selected sponsor and three mentors offering distinct content expertise. This research is nested within a larger, comprehensive training program including coursework as well as opportunities for teaching and professional development.