Is mammography screening beneficial: An individual-based stochastic model for breast cancer incidence and mortality

The benefits of mammography screening have been controversial, with conflicting findings from various studies. We hypothesize that unmeasured heterogeneity in tumor aggressiveness underlies these conflicting results. Based on published data from the Canadian National Breast Screening Study (CNBSS), we develop and parameterize an individual-based mechanistic model for breast cancer incidence and mortality that tracks five stages of breast cancer progression and incorporates the effects of age on breast cancer incidence and all-cause mortality. The model accurately reproduces the reported outcomes of the CNBSS. By varying parameters, we predict that the benefits of mammography depend on the effectiveness of cancer treatment and tumor aggressiveness. In particular, patients with the most rapidly growing or potentially largest tumors have the highest benefit and least harm from the screening, with only a relatively small effect of age. However, the model predicts that confining mammography to populations with a high risk of acquiring breast cancer increases the screening benefit only slightly compared with the full population.Author summary: We developed a mathematical model of breast cancer incidence and mortality in a population based on the CNBSS. All but three of the parameters could be estimated independently from the literature or taken from the CNBSS report, with the remaining ones calibrated to the outcomes of the CNBSS. The model includes three forms of heterogeneity: tumor aggressiveness describing the growth rate, maximum tumor size and age. The treatment response is personalized to a certain extent through dependence of the hazard rate of cancer mortality on tumor aggressiveness and detected tumor size. The model accurately matches the cancer incidence and survival in the CNBSS. We then used the model to quantify the benefit and harm of mammography screening, with benefit measured as the increase in 25-year survival, and harm as the increase in overdiagnosis.