Breast density and collagen alignment as predictors of DClS disease-free survival

DCIS诊断率的升高是当前乳腺癌筛查所固有的 乳腺癌的筛查-近30%的筛查发现的乳腺癌是DCIS。由于自然历史的不确定性 在DCIS中，人们普遍担心过度治疗。不幸的是，目前不可能 确定哪些DCIS病变可能进展到潜在致命的侵入性阶段。因此，当前 指南建议对所有患有DCIS的女性进行相对积极的治疗，包括手术，放疗， 并考虑进行激素治疗为了优化乳腺癌筛查过程，迫切需要 需要识别DCIS预后标志物，以允许个性化治疗策略。 乳腺摄影乳腺密度是一个很有前途的候选者，作为一个预后指标，预测的可能性， 从DCIS发展为侵袭性疾病。然而，目前只有很少的数据， 乳腺密度和疾病进展之间的联系，以及我们对乳腺癌的认识 乳腺密度的生物学机制。胶原蛋白是乳房密度的主要成分， 实验室研究表明，它在促进肿瘤侵袭中起关键作用。我们的目标是 建议将这些实验室发现转化为乳腺密度发展的进展， DCIS的预后标志物。我们的目标是：1）确定乳房X线摄影乳腺密度与乳腺癌之间的关系， DCIS女性患者的无病生存率; 2）确定胶原蛋白 DCIS女性的重组和无病生存率; 3）评估是否与DCIS女性之间的关系。 乳腺摄影乳腺密度和无病生存率之间的关系是由胶原重组介导的。到 为了实现这些目标，我们将使用佛蒙特州乳腺癌监测系统的数据和组织， 其中包括相关的患者风险因素，乳房X光检查，病理学，治疗和癌症结果数据， 约1,400例DCIS病例，随访时间长达16年。我们将使用三种不同的测量方法， 乳腺密度：分类BIF^DS评估，2-D定量计算机辅助方法（积云）， 和3D定量体积密度评估，其允许在特定情况下测量乳房密度， 邻近DCIS病变的感兴趣区域。多光子显微镜将用于评价胶原蛋白 在存档的DCIS肿瘤标本中进行重组。这项研究将评估乳腺X线摄影的潜力 乳腺密度和胶原重组作为识别DCIS病例的潜在标志物， 可能进展或仅需最小干预即可治疗。这可能会导致一个重大的 提高我们的能力，以尽量减少乳腺癌筛查（过度治疗）的危害，同时保持 益处（降低乳腺癌发病率和死亡率）。

Elevated rates of DCIS diagnoses are inherent to current breast cancer screening processes - almost 30% of screen-detected breast cancers are DCIS. Due to uncertainty in the natural history of DCIS, there is widespread concern regarding overtreatment. Unfortunately, it is currently impossible to determine which DCIS lesions are likely to progress to a potentially lethal invasive stage. Thus, current guidelines recommend relatively aggressive treatment for all women with DCIS, including surgery, radiation, and consideration of hormone therapy. To optimize the breast cancer screening process, there is an urgent need for identification of DCIS prognostic markers that would permit personalized treatment strategies. Mammographic breast density is a promising candidate as a prognostic marker to predict the likelihood of progression from DCIS to invasive disease. Currently, however, there Is only scarce data regarding the nature of the association between breast density and disease progression, and much uncertainty in our understanding of the biological mechanisms of breast density. Collagen is a major component of breast density and laboratory studies have shown that it plays a key role in facilitating tumor Invasion. The objective of our proposal is to translate these laboratory findings into advances in the development of breast density as a prognostic marker for DCIS. We aim to 1) determine the association between mammographic breast density and disease-free survival among women with DCIS; 2) determine the association between collagen reorganization and disease-free survival among women with DCIS; and 3) assess whether the association between mammographic breast density and disease-free survival is mediated by collagen reorganization. To accomplish these aims, we will use data and tissue from the Vermont Breast Cancer Surveillance System, which includes linked patient risk factor, mammography, pathology, treatment, and cancer outcomes data for approximately 1,400 DCIS cases with up to 16 years of follow-up. We will use three different measures of breast density: the categorical BIF^DS assessment, a 2-D quantitative computer-assisted method (Cumulus), and a 3-D quantitative volumetric density assessment that permits measurement of breast density in specific regions of interest adjacent to the DCIS lesion. Multiphoton microscopy will be used to evaluate collagen reorganization in archived DCIS tumor specimens. This study will evaluate the potential for mammographic breast density and collagen reorganization to serve as potential markers for identifying DCIS cases that are not likely to progress or could be treated with only minimal intervention. This could lead to a substantial improvement in our ability to minimize the harms of breast cancer screening (overtreatment) while preserving the benefits (reductions in breast cancer morbidity and mortality).