The Importance of Observational Evidence to Estimate and Monitor Mortality Reduction From Current Breast Cancer Screening

Plain Language Summary

The benefits and harms of breast cancer screening have been debated for many years. One reason this debate continues is continuing uncertainty about the magnitude of these benefits and harms. In the past, decision makers have relied on randomized controlled trials (RCTs) to give us the best estimates of the benefit of screening—the breast cancer mortality reduction attributable to screening. However, these RCTs were conducted from 20 to 50 years ago. In that time several important factors have changed: women’s breast cancer risk, screening technology, and breast cancer treatment. These factors could change the benefit of screening. Thus, we need current evidence about the reduction in breast cancer mortality from present-day screening. Because of the time required, the cost, and other inherent limitations of RCTs, this study design is not up to the task of providing this necessary information in a timely and ongoing manner.

A number of observational studies have recently been conducted to help us better understand the effect of mammography in today’s setting on breast cancer mortality. Unfortunately, these studies also have serious methodological limitations. A systematic review of the best of these studies shows much variation in their results. The best estimate from all of these studies is that current mammography is associated with about a 10% relative reduction in breast cancer mortality, which is less than predicted by the older RCTs. But this estimate is also not conclusive, and is likely to change in the future.

There is a need for an international team of experts to develop standards for higher-quality observational studies so that the effect of screening on breast cancer mortality can be better estimated and monitored over time.

Introduction

To make decisions about whether to start or continue widespread screening programs, and how intensive the screening should be, policy-makers need information about the current benefits and harms of screening. Clinicians need the same information to help their patients make individual decisions about screening. But we live in a constantly changing world, and what we thought we knew before rapidly becomes out of date and less relevant for today’s decisions. Screening programs, like all other facets of health care, need to be evaluated at the beginning, and then constantly monitored as key factors change over time. Programs once regarded as high value (ie, providing benefits that clearly justify the harms and costs) may become lower value as the risk of populations, screening technology, and treatment change.

It is important to require a high level of evidence about benefits and harms before implementing a widespread screening program at a particular intensity, and the same level of evidence to determine, periodically, whether the program should be continued at its current intensity. This high level of evidence is needed for at least three reasons: (1) the benefits of screening are often smaller than many would guess, and they may become even smaller over time; (2) the harms of screening are often larger than many would expect, and may grow over time; and (3) the costs of a full screening program are actually larger than many would suspect, and may increase over time. Screening programs that are implemented or continued without adequate supporting evidence may cause more harm than good and drain resources from other important health priorities.

It has been thought that the highest evidence requirement for a screening program is a RCT of screening. But because of several inherent limitations of RCTs of screening, and because of the need for ongoing monitoring, this chapter will suggest that implementation of a new screening program, and determination of whether to continue an existing program at its current intensity, should require both an RCT of screening and adequate observational evidence to determine that the benefits of a specific screening strategy clearly outweigh the harms and costs (ie, that it is high value). One, or even several, RCTs of screening without appropriate observational evidence from screening implementation are not enough. Further, prior to implementation or continuation, there should also be a determination of the extent to which the screening program at its proposed intensity would reduce the societal burden of the condition, and whether the cost and effort of the program would be more wisely spent in another way that would have a greater effect on reducing societal burden from the same condition or other health problems. The screening programs that should be implemented or continued are the ones that are both high value (ie, provide—for the people screened—benefits that clearly outweigh the harms and costs) and also relieve a substantial part of society’s burden of suffering from the condition.

These suggestions together would lead to a slowing down of implementation of new screening proposals (eg, adjunctive screening for women with dense breasts; changing primary screening from digital mammography to tomosynthesis), and perhaps a rolling back of the intensity of some existing programs. The intent is to increase the certainty that screening as currently practiced or proposed would actually lead to the wise use of resources to improve the health of the public without unduly increasing the harms of intensive health care.

Breast cancer screening has been implemented in many developed countries over the past 50 years, yet questions about the value of intensive screening and the extent to which this screening reduces the societal burden of breast cancer, remain, and may even be growing in importance. At least two of the reasons for this ongoing discussion may be an increasing awareness of the harms of screening, and an increasing concern that changes in population risk, screening technology, and treatment may make the results of the multiple screening RCTs less applicable to today. Although investigators have conducted many observational studies to help estimate current benefits and harms, these studies also have multiple methodologic challenges, and have yet to gain the full confidence of decision makers. The time has arrived when we should reexamine whether to continue breast cancer screening at its current level of intensity.

This review will examine the advantages and disadvantages of the older RCTs of breast cancer screening and the more recent observational evidence in assessing the current balance of benefits and harms of breast cancer screening. It will also make suggestions about how we might improve our evidence base to make better decisions about the appropriate intensity of breast cancer screening programs in the future.