Real and artificial controversies in breast cancer screening

Abstract

SUMMARYWe review the apparent disparities between different reviews of the effects of mammographic screening on mortality from breast cancer and overdiagnosis. When results of each review are expressed with respect to a common population and a common baseline, all find a substantial mortality benefit and variation among estimates is minor. There are genuine disagreements about overdiagnosis, but methods that take account of lead time and underlying incidence trends yield estimates of overdiagnosis that are modest and are outweighed by the mortality benefit. There is potential for individualized screening regimens, particularly with respect to breast density. Mammographic screening prevents deaths from breast cancer and can be recommended.When expressed in terms of breast cancer mortality in women of average UK risk, screened regularly from the age of 50-69 years, the major reviews indicate a reduction in breast cancer mortality in the range of one life saved per 64-257 women screened.Offering screening on the basis of age (starting at either 40 or 50 years) is an effective strategy.There is scope for varying the surveillance regimen (including the imaging technology) based on family history or breast density.

The Value of Modern Mammography Screening in the Control of Breast Cancer: Understanding the Underpinnings of the Current Debates

“…While conclusions about whether or not mammography screening can be recommended on the basis of a balance sheet of estimated benefits and harms may seem to be uncomplicated, the underlying data supporting the estimates may not be evident or well understood. Differences in the mortality reduction associated with screening can differ more than 4-fold (25,26), the number needed to invite/screen to save one life differ more than 20-fold (27,28), and estimates of overdiagnosis range from 0% to greater than 50% (29). At the core of the extreme views against the value of mammography are challenges to the credibility of the experimental evidence (11), trend data of published incidence and mortality rates (30,31), and claims of very high rates of overdiagnosis and overtreatment (32,33).…”

“…Closer examination reveals that each measure of absolute risk differs in terms of the reference population, mortality benefit (originally a 19% mortality reduction became 15% in the Nordic Cochrane Institute's estimate), duration of screening and followup, and whether invitation or exposure to screening is being compared. In particular, the most extreme estimate of the NNI to save one life is from the Nordic Cochrane Institute, which is influenced by the shortest observation period (10 years of screening with no follow-up beyond that) and an absolute benefit estimated from a subset of the RCTs that are dominated by women in their 40s (28). In an effort to understand the disparity between estimates in absolute benefit, given the similarity of the common relative risk estimates derived from the RCTs, Duffy and colleagues standardized the Nordic Cochrane Institute, USPSTF, and EUROSCREEN estimate of absolute benefit to a common scenario, that is, the recent UK Independent Panel estimate of the effect of screening on UK every 3 years in women ages 50 to 69 years on breast cancer mortality from ages 55 to 79 years.…”

Beyond the Mammography Debate: A Moderate Perspective

“…Individual thresholds show wide variance in such cases of fuzzy judgments, leading to indeterminate disagreements. And as noted in my editorial in this issue, is 1904 as the number needed to invite to prevent one bca death (uspstf estimate) substantively different in acceptance from 111-143 as the number needed to screen to prevent 1 bca death (euroscreen estimate) 58 ? Close to 2000 women subjected to the potential harms of screening has seemed in the literature and to many readers a far more sobering price to pay than fewer than 200, although in fact, once normalized to the same age period and duration for screening and to the same age range for detection of mortality prevention, the normalized numbers differ only modestly and cluster below 200.…”

“…This is true however-a large proviso-only if we accept that, for reliable estimation, the length of follow-up required to assure no significant overestimation of overdiagnosis and to adjust for the potential bias from residual detection leadtime effects is 25 years or more of follow-up, as elegantly demonstrated by Stephen Duffy and Dharmishta Parmar 55 using a well-motivated exponential sojourn time model. Such a model helps to account for the wide variation in estimates of overdiagnosis [56][57][58][59][60][61] , but such follow-up is no easy requirement to meet.…”

Through a Glass Darkly: The Mammography Debate

“…However, Stephan Duffy and colleagues 7 have ingeniously "normalized" these disparate findings to the same endpoint (using estimates from the Independent U.K. Panel on Breast Cancer Screening as the commonality), providing the numbers needed (to invite or to screen) to prevent 1 breast cancer death at ages 55-79 among screening U.K. women 50-69 years of age for 20 years. For uspstf, the number (needed to invite) was 193; for euroscreen, the number (needed to screen) was 64-96.…”