How best to determine the mortality benefit from screening mammography: dueling results and methodologies from Canada.

In this issue of the Journal, Coldman et al. report results from the Pan-Canadian Study of Mammography Screening and Mortality from Breast Cancer, an analysis of observational data from seven of 12 provincial screening programs from 1990 to 2009 (1). They find that " participation in mammography screening programs in Canada was associated with substantially reduced breast cancer mortality, " with a relative risk reduction of 40%. Interestingly, five of the seven provinces involved in this study were also sites for the Canadian Breast Screening Study (CNBSS), a randomized controlled trial (RCT) that recently reported, after 25 years of follow-up (1980 to 2005), no reduction in breast cancer mortality from screening mammography (2). If we are to determine the mortality benefit from current breast cancer screening, and to monitor it over time, we need to understand the lessons from the fascinating contrast presented by these two studies. In addition to the common setting, many aspects of the two studies were similar. In the Pan-Canadian provincial study, women ages 40 (five provinces started at 50) to 79 years (five provinces stopped at 69) self-referred for screening; in the CNBSS, women ages 40 to 59 years volunteered to be randomized. Mammography in the two studies appears to have been similar: two-view, single-read, analog mammography. CNBSS screened annually for five years; the provincial screening programs screened biennially (two provinces screened women aged 40–49 years annually). CNBSS included clinical breast examination (CBE) in some screening arms; some provinces used CBE and some didn't. Referral to treatment in both studies was determined by primary care physicians. The study methodologies, however, were quite different. The CNBSS was an RCT, assuring similarity of compared groups by randomization. The provincial study, on the other hand, is an observational study that pulls together data from each of the seven screening programs, provincial cancer registries, and provincial mortality databases in an attempt to compare observed breast cancer mortality among " participants " with expected mortality if they had not been screened. They derive their estimate of expected mortality from a multistep indirect approach using data from " nonpar-ticipants. " As the authors are aware, this indirect approach is prone to error at each step: adjusting for out-migration, deconstructing total provincial breast cancer incidence rates into specific rates for participants and for nonparticipants, deconstructing breast cancer survival rates in the same way, reconstructing incidence and survival data with appropriate demographic and …