A novel case‐control design to estimate the extent of over‐diagnosis of breast cancer due to organised population‐based mammography screening

Dear Sir, Beckmann et al. describe a new method for estimation of OD within a modern breast screening program. They propose the method has advantages over other observational approaches in that it (i) provides more accurate estimation of exposure to screening by using individual (rather than aggregate) data, (ii) avoids assumptions about lead time, and (iii) provides information which is useful to inform women. Although we commend their work toward a new method to measure OD in contemporary screening, we disagree with the advantages which they propose characterise the new method. The method estimates the impact of one screen on the cumulative incidence of breast cancer, based on the odds of exposure to screening among cases and controls, calculated in time intervals since the last screen against a reference standard group comprised of never screened cases and controls. As such, it estimates the overdiagnosis attributable to one screen, not of regular participation in screening. This is a critical point, because the estimate of OD (8% for invasive breast cancer and 14% for all breast cancer) would need to be modified (upward) to estimate the impact of participation in repeated screening rounds. Furthermore, there may be considerable misclassification of exposure because exposure to screening outside the national program in SA is not included, and the authors note a quarter of the population have participated in screening outside the public program. Hence, the new method may not provide more accurate estimation of exposure, nor a more valid estimate of the effect of exposure to screening. We agree that a potential strength of the new method is avoidance of assumptions about lead time. However, we suggest the comparison of cases and controls categorised in time intervals since the last screen against a reference category of never screeners may introduce bias. This is because the (reduced) incidence between screens may not have time to return to the same incidence as in never screeners before the next screen occurs. Using never screened women for comparison may underestimate the height of the incidence peak after the previous screen and overestimate both the depth of the trough and the time it takes for incidence to return to the never screened rate. As such it will artificially prolong the lead time duration. This complex issue is important to consider because of the profound effect of estimations of lead time on estimates of overdiagnosis, as recently debated in the literature. We disagree that this method provides useful information to inform women. The impact of the biases we have discussed may result in considerable underestimation of the risk of overdiagnosis among women who choose to participate in a program of regular screening over many screening rounds. We agree with the Independent UK Panel on Breast Cancer Screening that women invited to screening should be given transparent information about the benefit and harms of screening over the next 20 years as this is the choice women face, not whether to participate once or never in screening.