Background: In recent years, biologically motivated continuous tumor growth models have been introduced for breast cancer screening data. These provide a novel framework from which mammography screening effectiveness can be studied. Methods:We use a newly developed natural history model, which is unique in that it includes a carcinogenesis model for tumor onset, to analyze data from a large Swedish mammography cohort consisting of 65,536 participants, followed for periods of up to 6.5 years. Using patient data on age at diagnosis, tumor size, mode of detection, as well as screening histories, we estimate distributions of patient's age at onset, (inverse) tumor growth rates, symptomatic detection rates, and screening sensitivities. We also allow the growth rate distribution to depend on the age at onset. Results:We estimate that by the age of 75, 13.4% of women have experienced onset. Based on a model which accounts for the role of mammographic density in screening sensitivity, we estimated median tumor doubling times of 167 days for tumors with onset occurring at age 40, and 207 days for tumors with onset occurring at age 60. Conclusions:With breast cancer natural history models and population screening data, we can estimate latent processes of tumor onset, tumor growth, and mammography screening sensitivity. We can also study the relationship between the age at onset and tumor growth rates.Impact: Quantifying the underlying processes of breast cancer progression is important in the era of individualized screening.

With the advent of nationwide mammography screening programmes, a number of natural history models of breast cancers have been developed and used to assess the effects of screening. The first half of this article provides an overview of a class of these models and describes how they can be used to study latent processes of tumour progression from observational data. The second half of the article describes a simulation study which applies a continuous growth model to illustrate how effects of extending the maximum age of the current Swedish screening programme from 74 to 80 can be evaluated. Compared to no screening, the current and extended programmes reduced breast cancer mortality by 18.5% and 21.7%, respectively. The proportion of screen-detected invasive cancers which were overdiagnosed was estimated to be 1.9% in the current programme and 2.9% in the extended programme. With the help of these breast cancer natural history models, we can better understand the latent processes, and better study the effects of breast cancer screening.

Mammography screening programs are aimed at reducing mortality due to breast cancer by detecting tumors at an early stage. There is currently interest in moving away from the age‐based screening programs, and toward personalized screening based on individual risk factors. To accomplish this, risk prediction models for breast cancer are needed to determine who should be screened, and when. We develop a novel approach using a (random effects) continuous growth model, which we apply to a large population‐based, Swedish screening cohort. Unlike existing breast cancer prediction models, this approach explicitly incorporates each woman's individual screening visits in the prediction. It jointly models invasive breast cancer tumor onset, tumor growth rate, symptomatic detection rate, and screening sensitivity. In addition to predicting the overall risk of invasive breast cancer, this model can make separate predictions regarding specific tumor sizes, and the mode of detection (eg, detected at screening, or through symptoms between screenings). It can also predict how these risks change depending on whether or not a woman will attend her next screening. In our study, we predict, given a future diagnosis, that the probability of having a tumor less than (as opposed to greater than) 10‐mm diameter, at detection, will be, on average, 2.6 times higher if a woman in the cohort attends their next screening. This indicates that the model can be used to evaluate the short‐term benefit of screening attendance, at an individual level.

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