Re: Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial
The evaluation of mammography impact on breast cancer mortality in this study poses major challenges that the primary analyses of disease-specific deaths do not overcome. Consequently, the primary mortality analyses which show no benefit of mammography during the screening interval are not as informative about mammography benefit as one might hope.
There are two mortality analyses.
The first looks at the breast cancer death rate restricted to the cases detected during the first five years (the screening period). This is the cumulative death rate in the population but only allows deaths from the cases diagnosed in the first five years. The analysis finds similar death rates on the two arms.
This seems strange because there were there were 666 cases on the mammography arm and 524 cases on the control arm. Thus, if, as the investigators conclude, mammography has no effect, we would actually expect a higher observed cumulative death rate on the mammography arm, unless all of the (142) excess cases are overdiagnosed which is unlikely. Thus, this analysis may bias results against mammography benefit.
The second mortality analysis looks at all breast cancer deaths. But this includes all the cases diagnosed after the screening period. If, after this point, screening behavior evolves similarly in the two arms then the accumulation of a comparable case population in each arm will lead to a dilution of any mortality effect.
In conclusion, both mortality analyses are likely to yield attenuated disease-specific mortality risk ratios even if there is a benefit of mammography.
Competing interests: No competing interests