Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Annual screening with mammography and breast examination did not reduce breast cancer mortality in women 40 to 49 years of age

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ACP J Club. 2003 Mar-Apr;138:38. doi:10.7326/ACPJC-2003-138-2-038

Related Content in this Issue
• Companion Abstract and Commentary: Review: Mammography reduces breast cancer mortality rates


Source Citation

Miller AB, To T, Baines CJ, Wall C. The Canadian National Breast Screening Study-1: breast cancer mortality after 11 to 16 years of follow up. A randomized screening trial of mammography in women age 40 to 49 years. Ann Intern Med. 2002;137:305-12. [PubMed ID: 12204013] (All 2003 articles were reviewed for relevancy, and abstracts were last revised in 2009.)


Abstract

Question

In women 40 to 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

Randomized (allocation concealed*), blinded (outcome assessors),* controlled trial with mean 13-year follow-up.

Setting

15 centers in Canada.

Patients

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

Conclusion

In women 40 to 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.

*See Glossary.

Sources of funding: 10 Canadian funding agencies.

For correspondence: Dr. A.B. Miller, Deutsches Krebsforschungszentrum, Heidelberg, Germany. E-mail a.miller@dkfz-heidelberg.de.


Table. Annual breast cancer screening including mammography vs usual care to prevent breast cancer mortality†

Years of follow-up Cumulative breast cancer mortality rates/10 000 persons Rate ratio (95% CI)
Mammography Usual Care
2 to 5 2.26 2.12 1.07 (0.75 to 1.52)
6 2.55 2.51 1.01 (0.73 to 1.41)
7 3.04 2.90 1.05 (0.78 to 1.42)
8 3.29 3.15 1.04 (0.78 to 1.40)
≥ 9 3.72 3.82 0.97 (0.74 to 1.27)

†All comparisons are not significant.


Commentary

At first glance, these 2 reports seem inconsistent: Miller and colleagues’ study is an update of the Canadian National Breast Screening Study, continuing to show no hint of benefit in women 40 to 49 years of age; Humphrey and colleagues’ review 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- to 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 vs 0.73 to 0.99) overlap widely. The absolute reduction in breast cancer mortality is low in all age groups. For women 40 to 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 to 49 years of age, the estimated benefit of mammography is small (15%, or < 1/10 000 breast cancer deaths prevented per y) and the evidence of benefit is weak, with confidence intervals nearly overlapping 1. The risk for 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 for radiogenic breast cancer will be further increased.

For women ≥ 50 years, the evidence of a 20% to 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 systems (6) or to develop predictive models with greater discriminatory power (7).

Laura Rees Willett, MD
Robert Wood Johnson Medical School
New Brunswick, New Jersey, USA


References

1. Christiansen CL, Wang F, Barton MB, et al. Predicting the cumulative risk of false-positive mammograms. J Natl Cancer Inst. 2000;92:1657-66. [PubMed ID: 11036111]

2. Gotzche PC, Olsen O. Is screening for breast cancer with mammography justifiable? Lancet. 2000;355:129-34. [PubMed ID: 10675181]

3. Feig SA, Ehrlich SM. Estimation of radiation risk from screening mammography: recent trends and comparison with expected benefits. Radiology. 1990;174:638-47. [PubMed ID: 2305043]

4. Kerlikowske K, Grady D, Barclay J, Sickles EA, Ernster V. Effect of age, breast density, and family history on the sensitivity of first screening mammography. JAMA. 1996;276:33-8. [PubMed ID: 8667536]

5. Su Y, Swift M. Mortality rates among carriers of ataxia-telangiectasia mutant alleles. Ann Intern Med. 2000;133:770-8. [PubMed ID: 11085839]

6. Stoutjesdijk MJ, Boetes C, Jager GJ, et al. Magnetic resonance imaging and mammography in women with a hereditary risk of breast cancer. J Natl Cancer Inst. 2001;93:1095-102. [PubMed ID: 11459871]

7. Rockhill B, Spiegelman D, Byrne C, Hunter DJ, Colditz GA. Validation of the Gail et al. model of breast cancer risk prediction and implications for chemoprevention. J Natl Cancer Inst. 2001;93:358-66. [PubMed ID: 11238697]

8. Moss SM, Cuckle H, Evans A, et al, for the Trial Management Group. Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years’ follow-up: a randomized controlled trial. Lancet. 2006;368:2053-60. [PubMed ID: 19161727]