Jung In Kim1,2, Jason P Fine2, Dale P Sandler3, Shanshan Zhao1. 1. From the Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC. 2. Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC. 3. Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC.
Abstract
BACKGROUND: Preinvasive cancer conditions are often actively treated to minimize progression to life-threatening invasive cancers, but this creates challenges for analysis of invasive cancer risk. Conventional methods of treating preinvasive conditions as censoring events or targeting at the composite outcome could both lead to bias. METHODS: We propose two solutions: one that provides exact estimates of risk based on distributional assumptions about progression, and one that provides risk bounds corresponding to extreme cases of no or complete progression. We compare these approaches through simulations and an analysis of the Sister Study data in the context of ductal carcinoma in situ (DCIS) and invasive breast cancer. RESULTS: Simulations suggested important biases with conventional approaches, whereas the proposed estimate is consistent when progression parameters are correctly specified, and the risk bounds are robust in all scenarios. With Sister Study, the estimated lifetime risks for invasive breast cancer are 0.220 and 0.269 with DCIS censored or combined. Without detailed progression information, a sensitivity analysis suggested lifetime risk falls between the bounds of 0.214 and 0.269 across assumptions of 10%-95% of DCIS patients progressing to invasive cancer in an average of 1-10 years. CONCLUSIONS: When estimating invasive cancer risk while preinvasive conditions are actively treated, it is important to consider the implied assumptions and potential biases of conventional approaches. Although still not perfect, we proposed two practical solutions that provide improved understanding of the underlying mechanism of invasive cancer.
BACKGROUND: Preinvasive cancer conditions are often actively treated to minimize progression to life-threatening invasive cancers, but this creates challenges for analysis of invasive cancer risk. Conventional methods of treating preinvasive conditions as censoring events or targeting at the composite outcome could both lead to bias. METHODS: We propose two solutions: one that provides exact estimates of risk based on distributional assumptions about progression, and one that provides risk bounds corresponding to extreme cases of no or complete progression. We compare these approaches through simulations and an analysis of the Sister Study data in the context of ductal carcinoma in situ (DCIS) and invasive breast cancer. RESULTS: Simulations suggested important biases with conventional approaches, whereas the proposed estimate is consistent when progression parameters are correctly specified, and the risk bounds are robust in all scenarios. With Sister Study, the estimated lifetime risks for invasive breast cancer are 0.220 and 0.269 with DCIS censored or combined. Without detailed progression information, a sensitivity analysis suggested lifetime risk falls between the bounds of 0.214 and 0.269 across assumptions of 10%-95% of DCIS patients progressing to invasive cancer in an average of 1-10 years. CONCLUSIONS: When estimating invasive cancer risk while preinvasive conditions are actively treated, it is important to consider the implied assumptions and potential biases of conventional approaches. Although still not perfect, we proposed two practical solutions that provide improved understanding of the underlying mechanism of invasive cancer.
Authors: Virginia L Ernster; Rachel Ballard-Barbash; William E Barlow; Yingye Zheng; Donald L Weaver; Gary Cutter; Bonnie C Yankaskas; Robert Rosenberg; Patricia A Carney; Karla Kerlikowske; Stephen H Taplin; Nicole Urban; Berta M Geller Journal: J Natl Cancer Inst Date: 2002-10-16 Impact factor: 13.506
Authors: Irene L Wapnir; James J Dignam; Bernard Fisher; Eleftherios P Mamounas; Stewart J Anderson; Thomas B Julian; Stephanie R Land; Richard G Margolese; Sandra M Swain; Joseph P Costantino; Norman Wolmark Journal: J Natl Cancer Inst Date: 2011-03-11 Impact factor: 13.506