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Annual screening with mammography and breast examination did not reduce breast cancer mortality in women 40–49 years of age
  1. Laura Rees Willett, MD
  1. Robert Wood Johnson Medical School
 New Brunswick, New Jersey, USA

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 QUESTION: In women 40–49 years of age, does annual screening with mammography, clinical breast examination (CBE), and breast self examination (BSE) instruction reduce breast cancer mortality to a greater extent than a single CBE and BSE instruction?

    Design

    Randomised (allocation concealed*), blinded (outcome assessors),* controlled trial with mean 13 years of follow up.

    Setting

    15 centres in Canada.

    Patients

    50 489 women who were 40–49 years of age and had no previous diagnosis of breast cancer, were not pregnant, and had not had mammography in the previous 12 months. 50 430 (99.9%) were included in the analysis.

    Intervention

    All women received an initial CBE and instruction on BSE and were allocated to annual screening comprising mammography, CBE, and instruction and evaluation on BSE (n=25 214) or to usual care (n=25 216).

    Main outcome measure

    Breast cancer mortality.

    Main results

    Analysis was by intention to treat. During the first 5 years after study entry, the groups did not differ for breast cancer mortality rates and did not differ at each successive year of follow-up to ≥9 years (table). 105 breast cancer deaths occurred in the mammography group and 108 in the usual care group. The study had 80% power to detect a 40% difference in breast cancer mortality between groups after 5 years.

    Annual breast cancer screening including mammography v usual care to prevent breast cancer mortality †

    Conclusion

    In women 40–49 years of age, annual mammography and breast self examination did not reduce breast cancer mortality more than a single breast examination and usual health care.

    Commentary

    At first glance, these 2 reports seem inconsistent: The study by Miller et al is an update of the Canadian National Breast Screening Study, continuing to show no hint of benefit in women 40–49 years of age; the review by Humphrey et al is a USPSTF meta-analysis extending a recommendation for mammography to this age group for the first time. Ironically, the Canadian study was judged to be the highest quality study of all those evaluated by the USPSTF. Even with >50 000 participants, the Canadian study did not have the power to detect a protective effect <40%; the USPSTF meta-analysis found a much smaller benefit of 15% in the 40–49 year age group. The 95% confidence intervals/credible intervals of the reduction in breast cancer mortality in the 2 studies (0.74 to 1.27 v 0.73 to 0.99) overlap widely. The absolute reduction in breast cancer mortality is low in all age groups. For women 40–49 years of age, it is estimated to be <1/10 000 per year. For older women, the benefit is slightly greater and the confidence intervals more clearly exclude the null result.

    At what price is this modest benefit obtained? Surprisingly, in the appendix the USPSTF states: “A systematic review of adverse effects was beyond the scope of our review”. The evidence for adverse effects includes false positive results, believed to occur in 6.5% of mammograms;1 radiogenic breast cancer, estimated by the USPSTF to negate <10% of the breast mortality benefit; and diagnosis and treatment of cancer that may not become clinically important. In the Canadian study, about 14% more diagnoses of in situ or invasive breast cancer occurred in the screened group than in the usual care group; this difference persisted to almost 10 years after the intervention ended. In 2 Swedish trials including older women, 35% more women received major surgery (mastectomy or lumpectomy) and 25% more women received radiation in the screened groups.2 These results suggest that this may be a more substantial problem than previously thought.

    How can we convey these results to our patients? For women 40–49 years of age, the estimated benefit of mammography is small (15%, or <1/10 000 breast cancer deaths prevented per year) and the evidence of benefit is weak, with confidence intervals nearly overlapping 1. The risk of false positive results is higher at this age, as is the potential for radiation carcinogenesis.3 The absolute benefit might be greater in women at high risk because of a positive family history. However, mammography has been shown to be less sensitive in this group,4 and if the family history results from inherited radiation sensitivity,5 the risk of radiogenic breast cancer will be further increased.

    For women ≥50 years, the evidence of a 20–25% relative benefit in breast cancer mortality is stronger and exceeds 1/10 000 per year. An important issue in this group is the discovery of cancer that might not have caused symptoms, especially in women with comorbid conditions and a limited life span.

    Unfortunately, it is clear that most breast cancer deaths will not be prevented by mammography at any age. Perhaps the enormous resources devoted to the debate, promotion, and provision of mammography could be better used to study the efficacy of more sensitive detection systems6 or to develop predictive models with greater discriminatory power.7

    References

    View Abstract

    Footnotes

    • For correspondence: Dr A B Miller, Deutsches Krebsforschungszentrum, Heidelberg, Germany. a.miller{at}dkfz-heidelberg.de

    • Abstract and commentary also appear in ACP Journal Club.

    • Sources of funding: 10 Canadian funding agencies.

    • *See glossary. Therapeutics

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