The Value of All-Cause Mortality as a Metric for Assessing Breast Cancer Screening

Although screening mammography has been demonstrated to contribute to reducing mortality due to breast cancer, some have suggested that reduced all-cause mortality should constitute the burden of proof for effectiveness. Using a microsimulation model of the development, detection, and treatment of breast cancer, it is straightforward to demonstrate that this is an unrealistic expectation for trials of practical size and period of observation, even where the reduction of breast cancer mortality is substantial. Estimates of all-cause mortality will depend not only on the efficacy of the screening intervention but also on the alignment between the age distribution of the effect of screening on reduction of deaths and that of the other major causes of death. The size of a randomized trial required to demonstrate a reduction in all-cause mortality will, therefore, depend on the length and timing of the observation period and will typically be at least 10 times larger than the size of a trial powered to test for a reduction in deaths due to breast cancer. For breast cancer, which represents a small fraction of overall deaths, all-cause mortality is neither a practical nor informative metric for assessing the effectiveness of screening.