Cochrane for Clinicians
Putting Evidence into Practice
Effect of Mammography on Breast Cancer Mortality
Am Fam Physician. 2011 Dec 1;84(11):1225-1227.
A 54-year-old woman is new to your practice and has never been screened for breast cancer. She is concerned about false-positive results, and wonders if mammography does more harm than good.
Do the potential benefits of mammography outweigh the potential harms?
Although mammography can lead to false-positive results, emotional stress, and unnecessary biopsies, it appears to reduce deaths from breast cancer by about 15 percent.1 (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)
Background: A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published, and national policies vary.
Objectives: To assess the effect of screening for breast cancer with mammography on mortality and morbidity.
Search Strategy: The authors searched PubMed (November 2008).
Selection Criteria: The authors selected randomized trials comparing mammographic screening with no mammographic screening.
Data Collection and Analysis: The authors independently extracted data. Study authors were contacted for additional information.
Main Results: Eight eligible trials were initially identified. The authors excluded a biased trial and included 600,000 women in the analyses. Three trials with adequate randomization did not show a significant reduction in breast cancer mortality at 13 years (relative risk [RR] = 0.90; 95% confidence interval [CI], 0.79 to 1.02); four trials with suboptimal randomization showed a significant reduction in breast cancer mortality (RR = 0.75; 95% CI, 0.67 to 0.83). The RR for all seven trials combined was 0.81 (95% CI, 0.74 to 0.87). The authors found that breast cancer mortality was an unreliable outcome that was biased in favor of screening, mainly because of differential misclassification of cause of death. The trials with adequate randomization did not find an effect of screening on cancer mortality, including breast cancer, after 10 years (RR = 1.02; 95% CI, 0.95 to 1.10) or on all-cause mortality after 13 years (RR = 0.99; 95% CI, 0.95 to 1.03). Numbers of lumpectomies and mastectomies were significantly larger in the screened groups (RR = 1.31; 95% CI, 1.22 to 1.42) for the two adequately randomized trials that measured this outcome; the use of radiation therapy was similarly increased.
Authors' Conclusions: Screening is likely to reduce breast cancer mortality. Because the effect was lowest in the adequately randomized trials, a reasonable estimate is a 15 percent reduction corresponding to an absolute risk reduction of 0.05 percent. Screening led to 30 percent overdiagnosis and overtreatment, or an absolute risk increase of 0.5 percent. This means that for every 2,000 women invited for screening over 10 years, one will have her life prolonged, and 10 healthy women who would not have been diagnosed if there had not been screening will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress for many months because of false-positive findings. It is not clear whether screening does more good than harm. To help ensure that women are fully informed of benefits and harms before they decide whether to attend screening, the authors have written an evidence-based leaflet for patients, which is available at http://www.cochrane.dk/screening/mammography-leaflet.pdf.
These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the original reviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minor editing changes have been made to the text (http://www.cochrane.org).
Breast cancer is the second most commonly diagnosed cancer (after skin cancer) in U.S. women.2 Most primary care physicians recommend screening mammography in women every one to two years starting at 40 to 50 years of age. Widespread use of mammography and improvements in breast cancer treatment are thought to be responsible for the drop in breast cancer mortality since about 1990.3 In 2009, the U.S. Preventive Services Task Force (USPSTF) reevaluated its recommendation on mammography that was released in 2002.4 After reviewing new and existing literature,5 the USPSTF now recommends against routine screening mammography in women 40 to 49 years of age, and encourages physicians to make the decision to screen these women on a patient-by-patient basis.6 The review accompanying the USPSTF recommendation found a mortality benefit in all women, but an increased number of false-positive results in women 40 to 49 years of age.7 Women in this age group also have a lower incidence of breast cancer. This Cochrane review examines the risks and benefits of mammography for all age groups.1
The authors examined eight clinical trials comparing the effect of mammography with no mammography on breast cancer mortality and morbidity. One trial was excluded because of bias. The excluded trial reported different socioeconomic profiles of the control and intervention groups, and had differing exclusion criteria for each group.8 The remaining seven trials (n = 600,000) were divided into two groups: three trials with adequate randomization that showed a 10 percent reduction in breast cancer mortality (not statistically significant), and four trials with suboptimal randomization that showed a 25 percent reduction in breast cancer mortality (statistically significant).
The problems with randomization included insufficient data to determine who was excluded from the intervention and control groups and why, and in some cases, insufficient information about how practices or participants were randomized. It was not clear if the Cochrane authors knew whether the trials had employed suboptimal randomization practices in every case, or whether there was insufficient information about every step of the process. If the latter is true, then the most conservative approach would be to exclude those trials from the analyses, although it is possible that some or all of the randomization practices in those trials were acceptable. The overall risk reduction in breast cancer mortality for all seven trials was statistically significant (19 percent), but the reduction in all-cause mortality was not statistically significant.
The authors expressed concerns about how the cause of death was ascertained in some studies (i.e., by researchers and experts who may have known whether the participant was in the intervention or control group, instead of using a cause-of-death registry). Most of the trials were initiated in the 1960s and 1970s. In the past 30 to 40 years, standards of data reporting for clinical trials have changed, as have breast cancer treatments and the quality of available mammography technology. Because of these improvements, it is not known whether the breast cancer mortality benefit would be similar if these trials were repeated today. It also is not known what proportion of participants in the control group underwent mammography outside of the study, raising the question of potential bias toward the null hypothesis (i.e., making the reduction in mortality appear closer to zero than it actually is).
The authors discussed potential harms from mammography: the emotional stress and biopsies associated with a false-positive result, and the potential for cardiovascular effects from radiation therapy for early-stage cancers, particularly ductal carcinoma in situ, which is often diagnosed by mammography and does not always progress or recur. However, despite the shortcomings of the trials, screening appears to lower breast cancer mortality.
The review points out that the benefits of mammography may not be as great as originally thought, and that the risks may be underestimated. However, other sources have found sufficient evidence to continue using mammography for breast cancer screening. The American College of Physicians concluded that mammography is beneficial, but that the magnitude of the benefit should be interpreted with caution.9 The American Cancer Society recommends annual mammography starting at 40 years of age,10 and a National Cancer Institute fact sheet states that mammography reduces deaths from breast cancer in women 40 to 74 years of age and especially in women 50 to 74 years of age.11 The USPSTF recommends routine biennial screening mammography in women 50 to 74 years of age.6
There is not enough agreement about the current evidence for mammography to recommend a change in practice based on this review alone. Primary care physicians should continue to recommend mammography every two years in women 50 to 74 years of age, and to individualize their recommendation in women 40 to 49 years of age and in women older than 74 years. When discussing the risks and benefits of mammography with patients, physicians should mention the risk of false-positive results, especially in younger women, and the stress those results may cause. Physicians should interpret evidence-based recommendations based on each patient's clinical situation.6
Address correspondence to Joanne E. Wilkinson, MD, MSc, at Joanne.Wilkinson@bmc.org. Reprints are not available from the author.
Author disclosure: Dr. Wilkinson has received grant funding from the American Cancer Society and the National Cancer Institute to conduct mammography research.
1. Gøtzsche PC, Nielsen M. Screening for breast cancer with mammography. Cochrane Database Syst Rev. 2011;(1):CD001877.
2. National Cancer Institute. Surveillance Epidemiology and End Results (SEER) stat fact sheets: breast cancer. http://seer.cancer.gov/statfacts/html/breast.html. Accessed April 20, 2011.
3. Berry DA, Cronin KA, Plevritis SK, et al.; Cancer Intervention and Surveillance Modeling Network (CIS-NET) Collaborators. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med. 2005;353(17):1784–1792.
4. U.S. Preventive Services Task Force. Screening for breast cancer: recommendations and rationale. Ann Intern Med. 2002;137(5 pt 1):344–346.
5. Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L; Trial Management Group. Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years' follow-up: a randomised controlled trial. Lancet. 2006;368(9552):2053–2060.
6. U.S. Preventive Services Task Force. Screening for breast cancer: the U.S. Preventive Services Task Force recommendation statement [published corrections appear in Ann Intern Med. 2010;152(3):199–200, and Ann Intern Med. 2010;152(10):688]. Ann Intern Med. 2009;151(10):716–726.
7. Nelson HD, Tyne K, Naik A, Bougatsos C, Chan BK, Humphrey L. Screening for breast cancer: an update for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151(10):727–737.
8. Roberts MM, Alexander FE, Anderson TJ, et al. The Edinburgh ramdomised trial of screening for breast cancer: description of method. Br J Cancer. 1984;50(1):1–6.
9. Cheng T, Freund KM, Lane SE, Ganschow P, Battaglia TA. Screening for breast cancer. American College of Physicians PIER database; 2009. http://pier.acponline.org/physicians/screening/s369/s369.html (subscription required). Accessed April 11, 2011.
10. American Cancer Society. Guidelines for the early detection of cancer. http://www.cancer.org/healthy/findcancerearly/cancerscreeningguidelines/american-cancer-society-guidelines-for-the-early-detection-of-cancer. Accessed April 20, 2011.
11. National Cancer Institute. Fact sheet. Mammograms. http://www.cancer.gov/cancertopics/factsheet/detection/mammograms. Accessed April 20, 2011.
The Cochrane Abstract is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Dr. Wilkinson presents a clinical scenario and question based on the Cochrane Abstract, followed by an evidence-based answer and a critique of the review. The practice recommendations in this activity are available at http://www2.cochrane.org/reviews/en/ab001877.html.
The series coordinator for AFP is Kenneth W. Lin, MD, Department of Family Medicine, Georgetown University School of Medicine, Washington, DC.
A collection of Cochrane for Clinicians published in AFP is available at http://www.aafp.org/afp/cochrane.
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