Breast-Cancer Screening SPECIAL REPORT Breast-Cancer Screening — Viewpoint of the IARC Working Group B. Lauby-Secretan and Others    In November 2014, experts from 16 countries met at the International Agency for Research on Cancer (IARC) to assess the cancer-preventive and adverse effects of different methods of screening for breast cancer. In preparation for the meeting, the IARC scientific staff performed searches of the openly available scientific literature according to topics listed in an agreed-upon table of contents. The full report is presented in volume 15 of the IARC Handbooks of Cancer Prevention. Clinical Pearls   What data is available to assess the effectiveness of contemporary mammographic screening? The IARC working group recognized that the relevance of randomized, controlled trials conducted more than 20 years ago should be questioned, given the large-scale improvements since then in both mammographic equipment and treatments for breast cancer. More recent, high-quality observational studies were considered to provide the most robust data with which to evaluate the effectiveness of mammographic screening. The working group gave the greatest weight to cohort studies with long follow-up periods and the most robust designs, which included those that accounted for lead time, minimized temporal and geographic differences between screened and unscreened participants, and controlled for individual differences that may have been related to the primary outcome. Analyses of invitations to screenings (rather than actual attendance) were considered to provide the strongest evidence of screening effectiveness, since they approximate the circumstances of an intention-to-treat analysis in a trial.   Is there evidence of a reduction in breast cancer mortality with mammographic screening? Some 20 cohort and 20 case–control studies, all conducted in the developed world (Australia, Canada, Europe, or the United States) were considered by the IARC working group to be informative for evaluating the effectiveness of mammographic screening programs, according to invitation or actual attendance, mostly at 2-year intervals. Most incidence-based cohort mortality studies, whether conducted in women invited to attend screening or women who attended screening, reported a clear reduction in breast-cancer mortality, although some estimates pertaining to women invited to attend were not statistically significant. Women 50 to 69 years of age who were invited to attend mammographic screening had, on average, a 23% reduction in the risk of death from breast cancer; women who attended mammographic screening had a higher reduction in risk, estimated at about 40%. Case–control studies that provided analyses according to invitation to screening were largely in agreement with these results. Morning Report Questions Q. Is there benefit to mammographic screening of women 70 to 74 years of age, and is there a benefit for those 40 to 44 years of age? A. In the IARC analysis, a substantial reduction in the risk of death from breast cancer was consistently observed in women 70 to 74 years of age who were invited to or who attended mammographic screening in several incidence-based cohort mortality studies. Fewer studies assessed the effectiveness of screening in women 40 to 44 or 45 to 49 years of age who were invited to attend or who attended mammographic screening, and the reduction in risk in these studies was generally less pronounced. Overall, the available data did not allow for establishment of the most appropriate screening interval. Table 1. Evaluation of Evidence Regarding the Beneficial and Adverse Effects of Different Methods of Screening for Breast Cancer in the General Population and in High-Risk Women. Q. What harms are associated with mammographic screening? A. Estimates of the cumulative risk of false positive results differ between organized programs and opportunistic screening. The estimate of the cumulative risk for organized programs is about 20% for a woman who had 10 screens between the ages of 50 and 70 years. Less than 5% of all false positive screens resulted in an invasive procedure. There is an ongoing debate about the preferred method for estimating overdiagnosis. After a thorough review of the available literature, the working group concluded that the most appropriate estimation of overdiagnosis is represented by the difference in the cumulative probabilities of breast-cancer detection in screened and unscreened women, after allowing for sufficient lead time. The Euroscreen Working Group calculated a summary estimate of overdiagnosis of 6.5% (range, 1 to 10%) on the basis of data from European studies that adjusted for both lead time and contemporaneous trends in incidence. The estimated cumulative risk of death from breast cancer due to radiation from mammographic screening is 1 to 10 per 100,000 women, depending on age and the frequency and duration of screening. It is smaller by a factor of at least 100 than the estimates of death from breast cancer that are prevented by mammographic screening for a wide range of ages. After a careful evaluation of the balance between the benefits and adverse effects of mammographic screening, the working group concluded that there is a net benefit from inviting women 50 to 69 years of age to receive screening.