Mammographic Density and Invasive Breast Cancer

描述（由申请人提供）： 最近发表的妇女健康倡议（WHI）临床试验的结果明确证实了以前的流行病学数据，这些数据表明，联合激素治疗与雌激素和孕酮（EPT）增加了乳腺癌的风险。虽然风险增加的幅度相对较小，但鉴于EPT使用的高流行率，受影响的病例数可能很大。由于总体风险增加相对温和，因此一些女性可能比其他女性更容易受到EPT的致癌作用。因此，具有可用于识别那些高风险EPT使用者的临床生物标志物将是有用的。理想的生物标志物应在EPT过程中足够早地可测量，以允许在升高的风险被表达为明显疾病之前停止。乳腺摄影密度（MD）的变化是一个有前途的候选人，这样的标志物。 使用根据既往WHI辅助方案开发的胶片数字化和密度测量基础设施，将收集WHI试验EPT组内所有浸润性乳腺癌病例的乳房X线照片，沿着3例来自相同人群的对照，按照治疗分配（EPT或安慰剂）、临床中心和种族进行匹配。将测量每例受试者在初始基线乳房X线摄影和随机化后首次随访乳房X线摄影时的密度变化。MD的测量和风险评估将由四名经验丰富的人类读者和自动计算机程序进行。本项目的主要目的是估计与MD变化相关的乳腺癌相对风险，确定与MD变化相关的乳腺癌风险增加是否与基线MD无关，确定分配至EPT的女性中归因于MD变化的乳腺癌病例比例，以及，确定EPT后MD变化是否解释了整个研究人群中与EPT相关的乳腺癌风险增加。 该项目的次要目的是测量乳腺癌的相对风险的差异，使用MD测量由四个有经验的观察员，并确定是否乳腺癌的相对风险，使用MD的变化评估的实验自动化计算机程序是由四个有经验的评估员使用既定的阈值技术估计。

DESCRIPTION (provided by applicant): Results from the recently published Women's Health Initiative (WHI) clinical trial have unequivocally confirmed previous epidemiologic data, which suggested that, combined hormone therapy with estrogen and progestin (EPT) increases risk of breast cancer. Although the magnitude of the risk increase is relatively modest, given the high prevalence of EPT use, the attributable number of cases affected is likely to be large. Because the overall risk increase is relatively modest, it is likely that some women are more susceptible to the carcinogenic effect of EPT than others. It would thus be useful to have a clinical biomarker that could be used to identify those high-risk EPT users. The ideal biomarker would be measurable early enough in the course of EPT to allow cessation before elevated risk is expressed as frank disease. Mammographic density (MD) change is a promising candidate for such a marker. Using the infrastructure for film digitization and density measurement developed under a previous WHI ancillary protocol, mammograms from all cases of invasive breast cancer within the EPT arm of the WHI trial will be collected along with 3 controls from the same population, matched by treatment assignment (EPT or placebo), clinical center, and ethnicity. Density changes over the initial baseline mammogram and the first follow-up mammogram after randomization for each participant will be measured. Measurements of MD and risk assessment will be made by four experienced human readers and an automated computer program. The primary aims of this project are to estimate the relative risk for breast cancer associated with a change in MD, to determine whether the increased breast cancer risk associated with MD change is independent of baseline MD, to determine the proportion of breast cancer cases attributable to MD change among women assigned to EPT, and, to determine whether post-EPT MD change explains the increased breast cancer risk associated with EPT within the entire study population. The secondary aims of this project are to measure the difference in relative risk of breast cancer using MD measurements made by four experienced observers and to determine whether relative risk of breast cancer using MD change assessed by an experimental automated computer procedure is comparable to that estimated by four experienced assessors using established thresholding techniques.