Elsevier

The Lancet

Volume 380, Issue 9855, 17–23 November 2012, Pages 1778-1786
The Lancet

Review
The benefits and harms of breast cancer screening: an independent review

https://doi.org/10.1016/S0140-6736(12)61611-0Get rights and content

Summary

Whether breast cancer screening does more harm than good has been debated extensively. The main questions are how large the benefit of screening is in terms of reduced breast cancer mortality and how substantial the harm is in terms of overdiagnosis, which is defined as cancers detected at screening that would not have otherwise become clinically apparent in the woman's lifetime. An independent Panel was convened to reach conclusions about the benefits and harms of breast screening on the basis of a review of published work and oral and written evidence presented by experts in the subject. To provide estimates of the level of benefits and harms, the Panel relied mainly on findings from randomised trials of breast cancer screening that compared women invited to screening with controls not invited, but also reviewed evidence from observational studies. The Panel focused on the UK setting, where women aged 50–70 years are invited to screening every 3 years. In this Review, we provide a summary of the full report on the Panel's findings and conclusions. In a meta-analysis of 11 randomised trials, the relative risk of breast cancer mortality for women invited to screening compared with controls was 0·80 (95% CI 0·73–0·89), which is a relative risk reduction of 20%. The Panel considered the internal biases in the trials and whether these trials, which were done a long time ago, were still relevant; they concluded that 20% was still a reasonable estimate of the relative risk reduction. The more reliable and recent observational studies generally produced larger estimates of benefit, but these studies might be biased. The best estimates of overdiagnosis are from three trials in which women in the control group were not invited to be screened at the end of the active trial period. In a meta-analysis, estimates of the excess incidence were 11% (95% CI 9–12) when expressed as a proportion of cancers diagnosed in the invited group in the long term, and 19% (15–23) when expressed as a proportion of the cancers diagnosed during the active screening period. Results from observational studies support the occurrence of overdiagnosis, but estimates of its magnitude are unreliable. The Panel concludes that screening reduces breast cancer mortality but that some overdiagnosis occurs. Since the estimates provided are from studies with many limitations and whose relevance to present-day screening programmes can be questioned, they have substantial uncertainty and should be regarded only as an approximate guide. If these figures are used directly, for every 10 000 UK women aged 50 years invited to screening for the next 20 years, 43 deaths from breast cancer would be prevented and 129 cases of breast cancer, invasive and non-invasive, would be overdiagnosed; that is one breast cancer death prevented for about every three overdiagnosed cases identified and treated. Of the roughly 307 000 women aged 50–52 years who are invited to begin screening every year, just over 1% would have an overdiagnosed cancer in the next 20 years. Evidence from a focus group organised by Cancer Research UK and attended by some members of the Panel showed that many women feel that accepting the offer of breast screening is worthwhile, which agrees with the results of previous similar studies. Information should be made available in a transparent and objective way to women invited to screening so that they can make informed decisions.

Introduction

After the recommendations made by Professor Sir Patrick Forrest in his report on breast screening in 1986,1 women have been invited to screening through the NHS Breast Cancer Screening Programme since 1988. Since screening was established in the UK, additional follow-up data have become available from the trials on which the Forrest Report recommendations were based and from other randomised trials. Moreover, many observational studies have assessed existing population screening programmes.

This additional information has stimulated a continuing debate about the potential benefits and harms of population breast screening. The debate has focused on the reduction in mortality attributable to screening, the numbers of women overdiagnosed, and the way that the risks and benefits are communicated to women invited for screening. The arguments have become polarised between those who believe that the benefit of a decrease in mortality outweighs the harms and those who believe the opposite. These contrasting views of the evidence have arisen partly from disagreements about the validity and applicability of the available randomised controlled trials of breast screening, and partly from questions about the usefulness and interpretation of observational data for breast cancer incidence and mortality.

The debate about the benefits and harms of breast screening is not unique to the UK and its breast cancer screening programmes. In 2002, the International Agency for Research on Cancer2 reviewed the evidence for breast screening and proposed recommendations for further research and the implementation of screening programmes. In 2009, the US Preventive Services Task Force re-examined the efficacy of various screening modalities. They recommended that women younger than 50 years do not need to be screened routinely and women aged 50–74 years should have biennial rather than annual screens.3 The Canadian Taskforce on Preventative Health Care updated their guidelines for breast screening in 2011, and concluded that the reduction in mortality associated with screening mammography is small for women aged 40–74 years at average risk of breast cancer.4 They also noted a greater reduction in mortality for women 50 years and older than for those younger than 50 years, and that the risk of overdiagnosis and biopsy might be greater for younger than for older women. They recommended that women aged 50–74 years be screened routinely, but stated that substantial uncertainty exists around the evidence for this recommendation.4 The Cochrane Review5 concluded that, despite their substantial methodological limitations, trials showed that screening reduced breast cancer mortality, but at the cost of substantial harm from overdiagnosis.

As a result of this debate, Professor Sir Mike Richards (National Cancer Director, England) and Dr Harpal Kumar (Chief Executive Officer of Cancer Research UK) asked Professor Sir Michael Marmot to assemble and chair an independent Panel to review the evidence for the benefits and harms of breast screening in the UK. The terms of reference of the Panel and the details of the membership and support for the Panel are available in appendix 1 of the full report.6 Although the Panel has substantial expertise in epidemiology and medical statistics and in current breast cancer diagnosis and treatment practices, no Panel member has previously published work on breast screening, which helps to ensure an objective and independent assessment of the evidence. A patient advocate was an integral member of the Panel.

The Panel reviewed the extensive published work and listened to testimonies from experts in the specialty who were the main contributors to the debate.6 The Panel focused on the effects of screening on mortality and overdiagnosis in the context of the UK breast screening programmes, which currently invite women aged 50–70 years for a screening mammography every 3 years. The Panel's full report6 provides substantial background information and references to the evidence and recommendations summarised in this Review.

Section snippets

Measurement of benefit

The aim of screening is to advance the time of diagnosis so that prognosis can be improved by earlier intervention. Earlier diagnosis leads to an increase in the apparent incidence of breast cancer and extends the time between diagnosis and death, even if screening does not confer any benefit. The appropriate measure of benefit, therefore, is the reduction in mortality from breast cancer in women offered screening compared with those who are not.

Randomised controlled trials

Randomised controlled trials potentially provide

Overdiagnosis

The major harm of screening considered by the Panel was that of overdiagnosis. Because cancers are detected earlier with screening, the cancer incidence is expected to be higher in screened women during the screening period. The period between detection of a cancer at screening and when it would have presented clinically is the lead time and is an inevitable part of screening. In theory, when screening stops, the cancer incidence should fall, so that by the end of the screening period plus lead

Ductal carcinoma in situ

Ductal carcinoma in situ is a malignant tumour that arises from the epithelial tissues of the breast and consists of neoplastic cells. However, these cells do not infiltrate beyond the limiting basement membrane and therefore remain within the ducts where they arose. Ductal carcinoma in situ is usually grouped by grade into high, intermediate, or low grade. Although the cells have the appearance of malignancy, they do not show invasiveness, so carcinoma in situ is not in itself a

Other harms

The Panel considered other harms but in less detail, not because they are unimportant, but because there is more agreement about their nature and magnitude.

Some women have pain with mammography, which is sometimes enough to deter them from further attendances. About 4% of women attending for screening are recalled for repeat mammography and possible biopsy.29 Of these women, nearly one in five will have cancer; of the remainder, nearly 70% will need only further imaging and 30% a biopsy (under

Conclusions

Breast screening extends lives. The Panel's review of the evidence on benefit suggests a 20% reduction in mortality in women invited to participate in a 20-year screening programme. A lot of uncertainty surrounds this estimate, but it represents the Panel's overview of the evidence. This reduction corresponds to one breast cancer death prevented for every 235 women invited to screening, and one death averted for every 180 women who attend screening. The breast screening programmes in the UK,

Policy recommendations

The Panel concludes that the UK breast screening programmes confer significant benefit and should continue. For each woman, the choice is clear. On the positive side, screening confers a reduction in the risk of mortality from breast cancer because of early detection and treatment. On the negative side, is the knowledge that she has perhaps a 1% chance of having a cancer diagnosed and treated that would never have caused problems if she had not been screened.

Clear communication of these harms

Research recommendations

In view of the uncertainties in the published results of the randomised trials, the Panel supports the ongoing meta-analysis of centrally collated individual patient data from all the randomised trials. The Panel also supports the use of randomised trials to investigate the balance of benefit to harm of breast cancer screening to women younger than 50 years and those older than 70 years. In view of the problems with estimation of the degree of overdiagnosis from existing published work, the

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