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先前的流行病学数据，即激素治疗与雌激素和孕激素(EPT)联合治疗会增加乳腺癌的风险。尽管风险增加的幅度相对较小，但考虑到EPT的高流行率，受影响的可归因性病例数量可能很大。由于总体风险增加相对较小，一些女性可能比其他女性更容易受到EPT致癌作用的影响。因此，有一个临床生物标记物可以用来识别那些高风险的EPT使用者，这将是有用的。理想的生物标志物应该是在EPT过程中足够早地进行测量，以便在风险升高表现为坦率疾病之前停止治疗。钼靶密度改变(MD)是一种很有前途的标志物。 使用根据之前的WHI辅助方案开发的胶片数字化和密度测量基础设施，WHI试验EPT组内所有浸润性乳腺癌病例的乳房X光照片将与来自相同人群的3名对照一起收集，并与治疗分配(EPT或安慰剂)、临床中心和种族相匹配。将测量每个参与者在初始基线乳房X光照片和随机后的第一次后续乳房X光照片上的密度变化。MD的测量和风险评估将由四名经验丰富的人类读者和一个自动计算机程序进行。这个项目的主要目的是估计与MD变化相关的乳腺癌的相对风险，确定与MD变化相关的乳腺癌风险增加是否独立于基线MD，确定分配到EPT的女性中可归因于MD变化的乳腺癌病例的比例，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。 该项目的次要目标是使用四名有经验的观察者进行的MD测量来衡量乳腺癌相对风险的差异，并确定通过实验性的自动化计算机程序评估的MD变化的乳腺癌的相对风险是否与由四名经验丰富的评估者使用既定的阈值技术估计的乳腺癌的相对风险相当。

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.