Quantitative interpretation of age-specific mortality reductions from the Swedish breast cancer screening trials

Background: Results from five Swedish randomized trials may provide the most conclusive evidence on the effect of mammographic screening and have been used to forecast the expected reduction in breast cancer mortality in other programs. However, those trials demonstrated different degrees of reduction. The interpretation of observed mortality reduction after long follow-up for women aged 40-49 years at trial entry is both important and controversial. Purpose: We estimated what percentage of the observed mortality reduction for women aged 40-49 years at entry into the five Swedish screening trials might be attributable to screening these women at 50 years of age or older. Moreover, we calculated the most likely percentage mortality reduction for specific screening programs if the Swedish results were generalized and analyzed whether characteristics of each trial might at least partly explain the observed differences in reductions among the trials. Methods: Each Swedish trial was simulated with one underlying computer simulation model (MISCAN--MIcrosimulation SCreening ANalysis) of the natural history of the disease and the performance of screening, taking into account nine important trial characteristics. Improvement in prognosis for screen-detected case patients was estimated with age-specific reduction for all trials and each trial design as a reference. Results: An expected 7% reduction in breast cancer mortality for women aged 40-49 years at trial entry (relative risk [RR] = 0.93) was determined by computer modeling, assuming no improvement in prognosis for cancers that are screen detected before 50 years of age. This result indicates that, of the overall 10% observed reduction (RR = 0.90) in the five Swedish trials analyzed, most (70%) of this reduction might be attributable to screening these women in later rounds after their 50th birthday. Using additional trial information, predictions of breast cancer mortality reduction in women 50 years or older might be 11% larger than previously expected, assuming that high-quality mammographic screening can be achieved in nationwide programs. For women aged 50-69 years at trial entry, the differences in expected versus observed mortality reduction among the trials are estimated to be relatively small. (Expected mortality reductions range from 24% to 32%.) Conclusions: Results from the Swedish randomized breast cancer-screening trials should be seen as more favorable regarding the effect of mammographic screening in reducing breast cancer mortality for women aged 50-69 years than was estimated earlier. Our analyses also suggest that the improvement in prognosis due to screening for women aged 40-49 years is much smaller than that for women aged 50 years or older. Approximately, 70% of the 10% observed reduction in breast cancer mortality (i.e., 7%) for women aged 40-49 years at trial entry might be attributable to a reduction due to screening these women after they reach age 50. Implications: Detailed screening data for the 40- to 49-year age group of all Swedish trials should be analyzed to specifically estimate the natural history and performance of screening in this age group.