Screening Mammography in Women 40 to 49 Years of Age: A Systematic Review for the American College of Physicians

Key Summary Points Meta-analyses of randomized, controlled trials demonstrate a 7% to 23% reduction in breast cancer mortality rates from screening mammography in women 40 to 49 years of age. Screening mammography is associated with an increased risk for mastectomy but a decreased risk for adjuvant chemotherapy and hormone therapy. The risk for radiation is small (30 to 200 breast cancer deaths occurred in an annual screening of 100000 women 40 to 49 years of age). Rates of false-positive mammograms are high (20% to 56% after 10 mammograms), but false-positive results have little effect on psychological health or subsequent mammography adherence. Although many women report pain at the time of mammography, few see pain as a deterrent to future screening. Breast cancer risk varies among women in their 40s and affects the absolute reduction in rates of breast cancer mortality and the absolute risk for false-positive results on screening mammography. Several decades after the first guidelines for breast cancer screening were published, the routine use of mammography among asymptomatic women remains a topic of considerable debate (1, 2). This debate surfaces occasionally on screening women 50 years of age or older but persists regularly for screening women in their 40s (3, 4). The persistence of this controversy suggests a level of unease with our current understanding of the benefits and risks of mammography and with how this understanding has been translated into screening recommendations. Understanding the risks and benefits of screening mammography among women in their 40s is important because of the critical position that breast cancer holds in that age group. In the United States, breast cancer is one of the most common causes of death for women in their 40s. In 2002, almost 5000 women between 40 and 49 years of age died of breast cancer, compared with the 6800 women who died of heart disease or 1500 women who died of HIV (5). However, despite the relative importance of breast cancer in this age group, the burden of breast cancer among women in their 40s is low for a population-based screening program. More than 98% of women will not develop breast cancer between 40 and 50 years of age, but they will be subject to the risks of population-based screening. Of the 44000 women who die of breast cancer each year, fewer than one fifth received their diagnoses between the ages of 40 and 49 years (6, 7). We describe the results of a systematic review of the benefits and risks for screening mammography among women 40 to 49 years of age. Currently, 8 published meta-analyses discuss the effect of mammography screening in women 40 to 49 years of age on breast cancer mortality rates (816). All but 1 demonstrate a reduction in mortality rates from screening mammography. Thus, we did not perform another meta-analysis of the effect of screening mammography on breast cancer mortality rates, but we reviewed briefly the benefits of mammography screening derived from published screening trials and meta-analyses. In addition, we focused on 2 areas that are less well-studied but may affect recommendations about screening mammography among women in this age group: 1) risks of mammography screening and 2) variation in the risks and benefits of mammography according to an individual woman's characteristics. Methods Data Sources We created a framework of the potential risks and benefits of screening mammography to guide the literature search (Figure). On the basis of the framework, we searched MEDLINE, Pre-MEDLINE, and the Cochrane Central Register of Controlled Trials for English-language publications. We conducted the initial searches in spring 2004 and updated them in May 2005. General search strategies included Medical Subject Headings (MeSH) terms mammography or breast neoplasms and mass screening, as well as the keywords mammography, screening, and breast cancer. We conducted additional searches for each individual risk or benefit by using appropriate keywords and MeSH terms. We reviewed the references of all selected articles to identify additional relevant articles. Figure. Risks and benefits of screening mammography. Numbers correspond to the risks and benefits outlined in the Table. Study Selection Although previous systematic reviews have largely focused on randomized, controlled trials of mammography screening to quantify the benefit of screening on breast cancer mortality rates, most evidence about risks and other benefits of mammography is derived from observational studies, primarily prospective cohort studies (Table). Thus, we included a wide range of study designs in our review, with the included studies depending on the question and the available evidence. We used meta-analyses to assess the effect of mammography screening on breast cancer mortality rates and the risk for a false-positive mammogram at a single screening; randomized, controlled trials and prospective cohort studies to assess the effect of mammography on breast cancer treatment and the cumulative risk for a false-positive mammogram; and both prospective and cross-sectional observational studies to assess the other risks of mammography. We excluded case series and ecological designs for all risks except for ductal carcinoma in situ (DCIS), because most published data on DCIS outcomes are derived from these study designs. In addition, we reviewed the available publications from the 8 original mammography trials and the published simulation models of the effect of radiation from mammography screening. When possible, we focused on evidence from studies of screening mammography in women in their 40s or analyses of this age group within larger cohorts. When this was not possible, we used studies of screening mammography in older women. In the case of multiple publications from the same study, we included only the most recent publication in our analysis. Table. Risks and Benefits of Screening Mammography For study selection, a study investigator reviewed abstracts of all primary research articles to determine whether the full-text article should be retrieved. We retrieved 873 full-text articles, and 2 investigators reviewed them. In addition to the publications from the original trials, 117 of these articles met inclusion criteria. Data Extraction and Quality Assessment Two investigators abstracted information about the study design, setting, study sample, measures, analysis, and results. When needed, we contacted authors to clarify questions about study design or results. We evaluated study quality by using the approach proposed by the Centre for Evidence-Based Medicine (www.cebm.net/levels_of_evidence.asp) (Appendix Table 1). The lead investigator adjudicated any disagreements between the reviewers about article content and quality. Appendix Table 1. Evidence-Based Medicine Review Score: Criteria Used to Assess Study Quality* Role of the Funding Source The review was conducted under contract with the American College of Physicians. The funding source had no role in the collection, analysis, or interpretation of the data or in the decision to submit the article for publication. Results Benefits Breast Cancer Mortality Many meta-analyses have combined the results of major mammography screening trials to assess the effect of screening on breast cancer mortality rates. The latest meta-analysis demonstrated that screening mammography every 1 to 2 years in women 40 to 49 years of age results in a 15% decrease in breast cancer mortality after 14 years of follow-up (relative risk, 0.85 [95% CI, 0.73 to 0.99]) (12). This effect size is very similar to that reported by most previous meta-analyses of women 40 to 49 years of age (8, 10, 13, 14, 16). It is smaller than the 22% reduction seen among women 50 years of age or older (relative risk, 0.78 [CI, 0.70 to 0.87]) (12). The meta-analysis did not include the recently published results of the United Kingdom trial of annual mammography screening in 160921 women in their 40s (relative risk, 0.83 [CI, 0.66 to 1.04]) (17). However, this estimate is so similar to the results of the meta-analyses that the findings are unlikely to substantively change. Nevertheless, the effect of mammography screening on breast cancer mortality rates for women in their 40s remains controversial for several reasons. These reasons include concern about the quality of the trials that found mammography to have the largest benefit, the interval until the mortality rate reduction began, and the validity of death due to breast cancer as the primary end point (2). We review each issue in the following sections. Study quality is important because high-quality studies are more likely to provide accurate estimates of the effect size. However, judging study quality is difficult because of imperfect reporting and lack of consensus on criteria for evaluating studies. Furthermore, high-quality studies are relatively uncommon. In the setting of screening mammography for women 40 to 49 years of age, previous meta-analyses differ in their assessment of study quality and study inclusion. The Cochrane meta-analysis (2) excluded all but 2 of the 8 trials that provided information about this age group (the Canadian trial and the Malm trial). The most recent meta-analysis, which was from the U.S. Preventive Services Task Force (12), included all trials but the Edinburgh trial. Other meta-analyses have included all 8 trials (10, 11, 13, 14, 16). To a great extent, these differences arise from different levels of concern about inadequate or inconsistent information in study publications, including variation in the numbers of participants in sequential reports; differences in baseline characteristics among groups; and lack of information about randomization procedures, date of trial entry, and other study characteristics. Although many of these concerns cannot be fully resolved, recent analyses and critical reviews support the argument that none of the trials is suf