Analytical Investigation of Breast Cancer Progression: DCIS, Overdiagnosis

描述（由申请人提供）：本资助提案针对癌症早期发现中出现的研究问题，特别强调乳腺癌的早期诊断。主要研究领域包括：(i)为乳腺导管原位癌（DCIS）的疾病进展建立一个随机模型；（ii）调查乳腺癌的自然史，包括估计临床前停留时间和前置时间分布的方法；（iii）开发一种调查疾病过度诊断的新方法。在美国，乳腺DCIS的诊断率随着乳房x线摄影筛查的普及而迅速上升。关于DCIS的自然历史我们所知甚少。然而，被诊断为DCIS的女性患浸润性乳腺癌（IBC）的风险较高。了解DCIS的自然历史，即它是如何发展的，是否以及何时会发展为IBC，将是DCIS管理必不可少的第一步。对DCIS的自然病史建模是具有挑战性的，因为没有“理想”的数据显示未经治疗的DCIS病例的DCIS进展。本研究的第一个主要目的是建立一个随机模型来评估DCIS的进展过程。该模型将利用美国监测流行病学和最终结果（SEER）和挪威的数据。另一个目的涉及对乳腺癌早期停留时间分布和与早期发现癌症相关的前置时间的理论研究。最后，提出了一种新的超诊断估计方法。它出现在疾病的早期发现，通过筛选程序发现病例，这些病例在一个人的一生中永远不会成为临床病例。目前乳腺癌的实际过度诊断水平

DESCRIPTION (provided by applicant): This grant proposal is targeted at research problems arising in the early detection of cancer with special emphasis on the early diagnosis of breast cancer. The principal research areas include:(i) Develop a stochastic model for the disease progression of breast ductal carcinoma in situ (DCIS), (ii) Investigate the natural history of breast cancer, including methods for estimating the pre-clinical sojourn time and lead time distributions and (iii) Develop a new method for investigating the over diagnosis of disease. The diagnosis of breast DCIS in the U.S. has risen rapidly consistent with the dissemination of mammographic screening. Little is known about the natural history of DCIS. However women diagnosed with DCIS are known to be at elevated risk for invasive breast cancer (IBC). Knowledge on the natural history of DCIS, i.e. how it develops, if and when it will progress to IBC, would be an essential first step to the management of DCIS. Modeling the natural history of DCIS is challenging as there are no "ideal" data on DCIS progression of untreated DCIS cases. The first main aim of this research is to develop a stochastic model to evaluate the DCIS progression process. This model will utilize the U.S. Surveillance Epidemiology and End Results (SEER) and Norwegian data. Another aim involves a theoretical investigation of the sojourn time distribution in the early stage of breast cancer and the lead time associated with early detection of cancer. The last aim develops a new method for over diagnosis estimation. It arises in the early detection of disease setting, by screening programs finding cases which would never have become clinical in one's life time. Currently the actual level of over diagnosis from breast cancer screening is in dispute. It is planned to develop a new statistical method for estimating over diagnosis. This method will be unique in that it will make use of the disease incidence data. Applications will be made using the data from the Norwegian Breast Cancer Screening Program. Overall the proposed research will contribute greatly to the management of DCIS in clinical practice and shed some light on ongoing debate of 'harms" of breast cancer screening.