Estimating the natural progression of non-invasive ductal carcinoma in situ breast cancer lesions using screening data

Abstract

Objectives: In addition to invasive breast cancer, mammography screening often detects preinvasive ductal carcinoma in situ (DCIS) lesions. The natural progression of DCIS is largely unknown, leading to uncertainty regarding treatment. The natural history of invasive breast cancer has been studied using screening data. DCIS modeling is more complicated because lesions might progress to clinical DCIS, preclinical invasive cancer, or may also regress to a state undetectable by screening. We have here developed a Markov model for DCIS progression, building on the established invasive breast cancer model.

Methods: We present formulas for the probability of DCIS detection by time since last screening under a Markov model of DCIS progression. Progression rates were estimated by maximum likelihood estimation using BreastScreen Norway data from 1995-2002 for 336,533 women (including 399 DCIS cases) aged 50-69. As DCIS incidence varies by age, county, and mammography modality (digital vs. analog film), a Poisson regression approach was used to align the input data.

Results: Estimated mean sojourn time in preclinical, screening-detectable DCIS phase was 3.1 years (95% confidence interval: 1.3, 7.6) with a screening sensitivity of 60% (95% confidence interval: 32%, 93%). No DCIS was estimated to be non-progressive.

Conclusion: Most preclinical DCIS lesions progress or regress with a moderate sojourn time in the screening-detectable phase. While DCIS mean sojourn time could be deduced from DCIS data, any estimate of preclinical DCIS progressing to invasive breast cancer must include data on invasive cancers to avoid strong, probably unrealistic, assumptions.

Keywords: DCIS; breast cancer; cancer screening; statistical models.