Integrating Mammograms in Analyses of Genes and Environment in Sisters (IMAGES)

将乳房 X 光检查融入姐妹基因和环境分析中（图像）

• 批准号: 9235542
• 负责人: Parisa Tehranifar
• 金额: $ 49.01万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-06 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9235542
• 关键词: Address; Affect; Age; Area; Behavior Therapy; Breast; Breast Cancer Model; Breast Cancer Risk Assessment Tool; Breast Cancer Risk Factor; Breast Cancer Surveillance Consortium; CA-125 Antigen; Categories; Cessation of life; Chemoprevention; Clinical; Clinical assessments; Cohort Studies; Data; Diagnosis; Discrimination; Enrollment; Environment; Epidemiology; Exposure to; Family; Family Cancer History; Family history of; First Degree Relative; Frequencies; Genes; Genetic; Genetic Markers; Genetic screening method; Genetic study; Heterogeneity; High Risk Woman; Incidence; Individual; Intervention; Investigation; Life; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of ovary; Mammographic Density; Mammography; Mastectomy; Measurement; Measures; Menopause; Methods; Modeling; Monitor; Nature; Operative Surgical Procedures; Ovariectomy; Performance; Population; Postmenopause; Premenopause; Prevention program; Prevention strategy; Preventive; Preventive Intervention; Preventive care; Probability; Prospective cohort; Puerto Rican; Radiology Specialty; Recommendation; Recording of previous events; Relative Risks; Research; Retrieval; Risk; Risk Assessment; Risk Estimate; Risk Factors; Risk stratification; Sister; Standardization; Statistical Models; Statutes and Laws; Surveillance Program; Time; Tissues; Woman; base; cancer risk; case control; clinical decision-making; clinical practice; clinical risk; cost; design; experience; follow-up; improved; malignant breast neoplasm; predictive modeling; prospective; rate of change; screening; success

ABSTRACT Accurate breast cancer risk assessment has the potential to distinguish women at higher risk who need enhanced screening, preventive or risk-reducing therapies and surgeries from women at lower risk who can be spared interventions that yield little benefit and may cause harm. Breast cancer risk assessment is currently hampered by limited precision and accuracy of existing risk prediction models. Women with a family history of breast (FHBC) have the greatest need for better risk assessment as they often receive the same clinical recommendations despite substantial heterogeneity in the underlying risk by the extent of FHBC. Integration of mammographic breast density (MBD), a strong and readily assessable risk factor for breast cancer, in combination with detailed FHBC data, offers an exceptional opportunity for enhancing existing risk assessment methods. MBD generally declines with age, but the rate of change varies considerably between women, and may be particularly important to breast cancer risk; we have demonstrated that women who remain at high MBD over time are more likely to be diagnosed with breast cancer than women whose MBD decreases. Attempts to improve risk prediction models by incorporating MBD has had limited success as studies have used one-time measures of MBD and included mostly postmenopausal women for whom the largest changes in MBD may have already occurred. We propose to investigate within-individual changes in MBD over a 10- year period in relation to incident breast cancer by the extent of FHBC (Aim 1), and evaluate how changes in MBD may improve several clinical risk prediction models (Aim 2) and clinical risk stratification forming the basis for risk-based surveillance and preventive care (Aim 3). We will address these aims by building upon the U.S. Sister Study, a prospective cohort of 50,884 women with one or more sisters diagnosed with breast cancer who were personally breast cancer-free at enrollment in 2003-2009; active annual follow-up is conducted for at least 10 years with each woman. Using a nested case-control design, we will retrieve existing mammograms for all incident breast cancer cases diagnosed at ages ≤ 60 years (n=1,242 cases to date) and controls matched on age and enrollment year (2 controls selected per case at the time of case identification). We will undertake a comprehensive assessment of MBD, using both clinically available qualitative measures used in clinical practice, and assessing quantitative measures that allow for measurement of smaller changes and different components of MBD (e.g., dense, nondense tissue) that are independently associated with breast cancer risk. Our team’s experience in leading studies of MBD and prospective available data in the Sister Study will afford an unparalleled investigation of prospective MBD changes in relation to breast cancer risk, modifiable and genetic factors, and how to use this information to enhance risk assessment in women with FHBC. These results are necessary to inform personalized risk-based surveillance and prevention programs.

摘要 准确的乳腺癌风险评估有可能区分哪些高危女性需要 加强筛查、预防或降低风险的治疗和手术，来自风险较低的妇女 避免了收效甚微、可能造成伤害的干预措施。乳腺癌风险评估目前正在进行 受制于现有风险预测模型的精确度和准确性有限。有家族史的妇女 乳房(FHBC)最需要更好的风险评估，因为他们经常接受相同的临床 建议，尽管潜在风险在FHBC的程度上有很大的异质性。集成 乳房X光摄影乳房密度(MBD)是乳腺癌的一个强有力的和容易评估的危险因素，在 结合详细的FHBC数据，提供了增强现有风险评估的绝佳机会 方法：研究方法。MMD一般会随着年龄的增长而下降，但不同女性的变化速度差别很大，而且 可能对乳腺癌风险特别重要；我们已经证明，处于高风险状态的女性 随着时间的推移，MBD比MBD减少的女性更有可能被诊断为乳腺癌。 通过纳入MBD来改进风险预测模型的尝试，正如研究所取得的那样，成效有限 使用一次性测量MBD的方法，主要包括变化最大的绝经后妇女 可能已经发生了MBD。我们建议调查MBD在10年内的个人变化- 年期间按FHBC范围(目标1)与发生的乳腺癌有关，并评价 MBD可能会改进几种临床风险预测模型(目标2)，并为临床风险分层奠定基础 用于基于风险的监测和预防护理(目标3)。我们将在美国的基础上实现这些目标。 姐妹研究，对50,884名有一个或多个姐妹被诊断患有乳腺癌的女性进行前瞻性队列研究 在2003-2009年间登记时个人没有患乳腺癌；积极的年度随访在 和每个女人在一起至少10年。使用嵌套病例对照设计，我们将检索现有的乳房X光照片 对于所有在60岁的≤确诊的乳腺癌病例(n=1,242例迄今)和对照 在年龄和登记年份上匹配(在病例识别时每个病例选择2个对照)。我们会 使用以下两种临床可用的定性指标对MBD进行全面评估 临床实践，以及评估允许测量较小变化和 与乳房独立相关的MBD的不同成分(例如致密和非致密组织) 癌症风险。我们团队在领导MBD研究方面的经验和Sister中的预期可用数据 这项研究将对未来MBD变化与乳腺癌风险的关系进行无与伦比的调查， 可改变的和遗传的因素，以及如何利用这些信息来加强对患有 FHBC。这些结果对于个人化的基于风险的监测和预防计划是必要的。