QUANTITATIVE INTERPRETATION OF AGE-SPECIFIC MORTALITY REDUCTIONS FROMTHE SWEDISH BREAST CANCER-SCREENING TRIALS

Background: Results from five Swedish randomized trials may provide th e most conclusive evidence on the effect of mammographic screening and have been used to forecast the expected reduction in breast cancer mo rtality in other programs, However, those trials demonstrated differen t degrees of reduction, The interpretation of observed mortality reduc tion after long follow-up for women aged 40-49 years at trial entry is both important and controversial, Purpose: We estimated what percenta ge of the observed mortality reduction for women aged 40-49 years at e ntry into the five Swedish screening trials might be attributable to s creening these women at 50 years of age or older, Moreover, we calcula ted the most likely percentage mortality reduction for specific screen ing programs if the Swedish results were generalized and analyzed whet her characteristics of each trial might at least partly explain the ob served differences in reductions among the trials, Methods: Each Swedi sh trial was simulated with one underlying computer simulation model ( MISCAN-MIcrosimulation SCreening ANalysis) of the natural history of t he disease and the performance of screening, taking into account nine important trial characteristics, Improvement in prognosis for screen-d etected case patients was estimated with age-specific reduction for al l trials and each trial design as a reference, Results: An expected 7% reduction in breast cancer mortality for women aged 40-49 years at tr ial entry (relative risk [RR] = 0.93) was determined by computer model ing, assuming no improvement in prognosis for cancers that are screen detected before 50 years of age, This result indicates that, of the ov erall 10% observed reduction (RR = 0.90) in the five Swedish trials an alyzed, most (70 %) of this reduction might be attributable to screeni ng these women in later rounds after their 50th birthday, Using additi onal trial information, predictions of breast cancer mortality reducti on in women 50 years or older might be 11% larger than previously expe cted, assuming that high-quality mammographic screening can be achieve d in nationwide programs, For women aged 50-69 years at trial entry, t he differences in expected versus observed mortality reduction among t he trials are extimated to be relatively small, (Expected mortality re ductions range from 24% to 32%.) Conclusions: Results from the Swedish randomized breast cancer-screening trials should be seen as more favo rable regarding the effect of mammographic screening in reducing breas t cancer mortality for women aged 50-69 years than was estimated earli er, Our analyses also suggest that the improvement in prognosis due to screening for women aged 40-49 years is much smaller than that for wo men aged 50 years or older, Approximately, 70% of the 10% observed red uction in breast cancer mortality (i.e., 7%) for women aged 40-49 year s 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.