Mark Helfand

The Cost-Effectiveness of Screening Mammography beyond Age 65 Years: A Systematic Review for the U.S. Preventive Services Task Force

Breast cancer is the second leading cause of potentially avoidable cancer death among women (1, 2). Breast cancer is largely found in older women (1, 3). Currently in the United States, almost 50% of new cases and nearly two thirds of deaths from breast cancer occur in 13% of the female population 65 years of age or older (hereafter referred to as older women) (1). By 2030, 1 in 5 U.S. women will be 65 years of age or older (4). This graying of America (5) will largely increase the absolute number of breast cancer cases among older women (6). However, since few older women were included in the original screening trials, we have few primary data on which to base recommendations. This rapidly growing population group is primarily heterogeneous, with important age-related variations in comorbid conditions (7-9), mammography sensitivity (10, 11), natural history of disease and tumor characteristics (for example, incidence of estrogen-receptorpositive tumors, which have a better prognosis, increases with age) (3, 12-16), and morbidity associated with breast cancer and treatments (16-18). Many of these factors differ in their potential influence on the costs and yields of screening older women. In such situations, cost-effectiveness analysis can summarize the expected benefits (life-saving potential and improved quality of life), harms (side effects), and costs of screening beyond age 65 years (19-21). Previous cost-effectiveness analysis of breast cancer screening has generally demonstrated that mortality can be reduced at reasonable costs per life-year saved among women 65 years of age and younger. It is unclear, however, whether screening is cost-effective for women 65 years of age and older (10, 22-27). We conducted a systematic review of published cost-effectiveness analyses to evaluate the costs and benefits of screening women beyond age 65 years to help the U.S. Preventive Services Task Forces deliberations about age limits for breast cancer screening. Methods The principles and rationale for our approach to conducting systematic reviews of cost-effectiveness studies have been described previously (28). We reviewed original economic evaluations of breast cancer screening that included data for older women. We sought studies addressing the incremental cost-effectiveness of screening beyond age 65 years compared with screening up to age 65 years. We searched MEDLINE from January 1989 to March 2002 and the National Health Service Economic Evaluation Database (agatha.york.ac.uk/nhsdhp.htm) from January 1994 to March 2002. We used the following search terms to capture studies related to breast cancer screening: exploded Medical Subject Headings (MeSH) terms breast neoplasms and mass screening, breast cancer and exploded MeSH term mass screening, and exploded MeSH term mammography. To limit the search to studies relevant to screening in older women, we added the MeSH term aged. We used different strategies in each database to identify cost-effectiveness analyses. For our MEDLINE search, we added the exploded MeSH term cost benefit analysis. In the National Health Service Economic Evaluation Database, we limited the search to economic evaluations. We chose 1989 as a starting point because it marked the time period in which papers on cost-effectiveness of breast cancer screening began to appear. To identify studies not captured by our database searches, we manually searched the reference lists of retrieved articles and contacted selected authors and experts in the field to identify additional studies. Two investigators independently reviewed each identified abstract, and potentially eligible articles were retrieved. Using information in the abstracts, we excluded studies that were not costutility analyses or cost-effectiveness analyses, such as economic evaluations that did not quantify the health outcomes achieved for a given cost. We also excluded studies that reported only cost per patient screened or cost per type of cancer detected; studies without original analyses; studies that did not allow assessment of screening after age 65 years; and studies that were not performed from a societal perspective or the perspective of a third-party payer, such as Medicare or a national health system. When several publications reported results from the same cost-effectiveness model, we included more than 1 study if the studies contained different information. If several articles presented the same analyses, we selected the most comprehensive analysis and used the other articles for supplemental information. When the decision about whether to include a study was unclear from the title and abstract, we evaluated the full article. A 4-member working group reached consensus on final inclusion or exclusion of articles. Excluded studies are summarized in an appendix that is available from the authors. One reviewer extracted data into evidence tables. Other members checked the results, and discrepancies were resolved by consensus. Data were abstracted on the basis of a modeling approach; screening intervals; the assumptions of each study about the epidemiology and natural history of breast cancer; estimates of variables related to the effectiveness of screening, including test accuracy, adherence rates, and complication rates; estimates of the costs of screening, diagnosis, and treatment; the proportion of types of cancer and cancer deaths prevented by screening; and the effect of varying key parameters (sensitivity analyses). For each study, we tabulated life-years gained and costs per person for different age groups. The evaluated strategies were ordered by effectiveness. Costs were updated to 2002 U.S. dollars by using the Consumer Price Index for medical care (29). Incremental cost-effectiveness ratios were then calculated, comparing screening after 65 years of age to screening cessation at 65 years of age. This report was funded by a contract to the Oregon Health and Science University Evidence-based Practice Center from the Agency for Healthcare Research and Quality (AHRQ) and a cooperative agreement from the National Cancer Institute. Staff of AHRQ reviewed the draft and final manuscript and made editing suggestions. Results Our initial searches identified 115 potentially relevant studies. Ten studies met our inclusion criteria and included specific data on the cost-effectiveness of screening older women (10, 22, 25-27, 30-34). The most common reasons for excluding the remaining articles were lack of data on screening after 65 years of age, study type other than a cost-effectiveness study, and duplicate publication. The Table shows the basic features of the 10 included studies. All were cost-effectiveness analyses with benefits expressed in life-days or life-years gained and costs expressed in U.S. (or other) dollars. Most studies expressed incremental results for extending screening to ages 75 or 80 years, compared with ceasing screening at age 65 years. Two studies presented results as an average for screening from ages 50 to 74 or 79 years (25, 34). Each study considered the direct costs of care, including the costs of screening, diagnostic tests, and treatment. No study considered patient time costs associated with screening, diagnostic, or surveillance procedures or treatment of cancer. All studies discounted costs and effects. Discount rates varied from 3% to 6%; the most common rate was 5%. The variables used in the different studies were similar to those noted in the U.S. Preventive Services Task Force summary of recommendations (35). Table. Summary of Studies on the Cost-Effectiveness of Screening for Breast Cancer after Age 65 Years Overall, despite methodologic differences, the cost-effectiveness results were fairly consistent. The results for biennial screening after age 65 years generally indicated incremental costs of approximately

Grading the strength of a body of evidence when comparing medical interventionsdAgency for Healthcare Research and Quality and the Effective Health Care Program

34 000 to

Evidence Brief: Effectiveness of Intensive Primary Care Programs

88 000 (2002 U.S. dollars) per life-year saved compared with stopping screening at age 65 years (Table); costs per life-year saved increased after age 65 years. It was also cost-effective to screen women after age 65 years if they had not been regularly screened before age 65 years (27, 32). Most studies considered the average risk for breast cancer, but 1 study specifically tested results by level of risk for breast cancer (based on bone mineral density and a proxy for lifetime estrogen exposure) (27). One study presented results separately for older black and white women (32), since black women have historically had lower screening rates and higher mortality rates than white women (1, 36). The remaining analyses explored results for women at average risk for breast cancer on the basis of population incidence and mortality rates. A key issue in evaluating the benefits of screening older women is that in this group, in addition to an increased risk for breast cancer, the probability of developing other illnesses that can decrease life expectancy is also higher, offsetting survival benefits of early cancer detection. For example, if a woman has a small breast tumor detected at screening but dies of a myocardial infarction the next year, screening had no benefit in extending life expectancy. Two papers in our review specifically addressed the effect of comorbid conditions on screening decisions (30, 32). One paper considered the situation for women with dementia (30), and the other assessed the influence of congestive heart failure and hypertension (32). These studies found that screening reduces breast cancer mortality in all but the sickest women. The remaining studies captured the effects of average numbers of comorbid conditions through use of general population mortality rates. Detecting cases of cancer or ductal carcinoma in situ that would not have become clinically evident or would not have progressed to invasive disease before death might be considered a screening-related harm or overdiagnosis. Depending on a womans preference, living for a longer period with the