Cost-Effectiveness of Extending Screening Mammography Guidelines To Include Women 40 to 49 Years of Age

There is universal agreement [1-4] that women 50 to 69 years of age should undergo screening mammography because randomized, controlled trials have shown that such screening reduces breast cancer mortality in this age group [5, 6]. This consensus is bolstered by the results of cost-effectiveness analyses that consistently show that this benefit can be achieved at a reasonable cost [7-9]. In contrast, whether women 40 to 49 years of age should undergo screening mammography is controversial [10-15]. Pooled results of large randomized, controlled trials have shown no mortality reduction in 40- to 49-year-old women after 7 to 9 years of screening [5, 16-18]. However, a statistically significant reduction in breast cancer mortality becomes apparent 10 to 14 years after the initiation of screening [19]. Some authors have argued that this delayed benefit should not be ignored [11]. However, the reality of constrained health care resources requires that any benefit from preventive services be achieved at a reasonable cost. Two recently published analyses [20, 21] suggest that mammographic screening in younger women may be as cost-effective as screening in older women. The first analysis [20] calculated average cost-effectiveness by comparing a strategy of screening 40- to 69-year-old women with no screening. Most of the benefit achieved by using this strategy occurs when women are 50 to 69 years of age. Therefore, this analysis did not address whether it is cost-effective to screen women from 40 to 49 years of age in addition to screening them from 50 to 69 years of age. To determine whether the additional benefit obtained by extending screening mammography to women 40 to 49 years of age comes at a reasonable cost would require an incremental cost-effectiveness analysis [22-26]. The second analysis [21] used a simplified life-expectancy accounting method, did not discount costs or benefits, and associated screening mammography with unsubstantiated mortality reductions (30% for the base case). Neither analysis [20, 21] included an important aspect of the results of screening mammography trials in 40- to 49-year-old women: that is, no benefit occurs until 10 years after the initiation of screening. An earlier analysis [10] found screening mammography to be more expensive in women 40 to 49 years of age than in women 50 years of age and older. This previous analysis calculated incremental cost-effectiveness, discounted costs and benefits, and included an estimated delay between the onset of screening and the onset of a mortality benefit. Our analysis extends this work by including updated pooled results of the randomized, controlled trials [19]; actual delay times before the onset of benefits; and updated costs of mammography and treatment of breast cancer. Methods Model We developed a Markov model [27, 28] that compared the life expectancy of women undergoing different breast cancer screening strategies. Except for women in whom breast cancer was diagnosed at the initiation of screening, women were healthy at entry into the model. At the end of each 1-year cycle, women were in one of four health states: They remained healthy, developed breast cancer and remained alive, died of breast cancer, or died of another cause. The transition probabilities [that is, the probabilities of developing breast cancer, dying of breast cancer, and dying of another cause] were both age- and strategy-dependent. The base-case analysis compared three strategies: 1) no screening; 2) screening biennially from 50 to 69 years of age; and 3) screening every 18 months from 40 to 49 years of age, followed by screening biennially from 50 to 69 years of age. The rationale for these screening intervals is discussed below. We calculated the cost-effectiveness of screening in women 50 years of age and older by comparing the first strategy with the second strategy. To determine the incremental cost-effectiveness of screening in 40- to 49-year-old women, we compared the second and third strategies. Costs and benefits were discounted at a rate of 3% per year for the base-case analysis [23]. Benefits Trials of screening mammography have shown no reduction in breast cancer mortality among screened women until several years after the initiation of screening [5, 18, 29, 30]. Meta-analyses and one pooled analysis have shown that among 40- to 49-year-old women, the summary relative risk reduction in breast cancer mortality 7 to 9 years after the initiation of screening is about 1, indicating no reduction in mortality [5, 16-18]. Ten to 12 years after the initiation of screening, a nonsignificant trend toward reduced mortality is evident in the screened group (Figure 1, left) [5, 18, 29, 30]. Recently updated results show a statistically significant 16% reduction that occurs 10 to 14 years after the initiation of screening [19]. For women 50 to 69 years of age, there is an initial period of about 5 years that shows no benefit from screening (Figure 1, right) [18, 29, 30]. Figure 1. Cumulative breast cancer mortality in screened (black circles) compared with nonscreened (white circles) women. Left. Right. In our model, for women who start screening at 50 years of age, a 27% reduction in breast cancer mortality (Table 1) [5] begins 5 years after the initiation of screening and continues until age 74 years. Although screening ends at 69 years of age, we assumed that women would continue to benefit for another 5 years because of early detection of breast cancer in the last years of screening. For women who begin screening at 40 years of age, a 16% reduction in breast cancer mortality starts at age 50 years; this reduction increases to 27% at age 55 years. Table 1. Information Used To Calculate Life Expectancy Screening Interval The screening interval in randomized, controlled trials of screening mammography has varied from 12 to 33 months for women 50 years of age and older. Pooled results of the efficacy of mammography stratified by length of screening interval do not differ for women in this age group [5]. From published results [5], we determined a 28% (95% CI, 15% to 31%) reduction in breast cancer mortality in women 50 years of age and older who were screened every 18 to 33 months and a 25% (CI, 1% to 43%) reduction in those screened every 12 months. For the base-case analysis, we therefore chose to perform biennial screening in women 50 years of age and older because screening more often only increases cost without increasing the benefits of screening. For the base-case analysis, we used the pooled reduction in breast cancer mortality (27%) [5] from all randomized, controlled trials to determine the cost-effectiveness of biennial screening in 50- to 69-year-old women; in a sensitivity analysis, we determined the cost-effectiveness of annual screening. The screening interval in randomized, controlled trials has varied from 12 to 24 months for women 40 to 49 years of age. Pooled results of the efficacy of screening mammography stratified by length of screening interval did not show a statistically significant reduction in breast cancer mortality for 12-month or 18- to 24-month screening intervals [5]. As noted above, recently reported pooled results of all randomized, controlled trials, which on average used a screening interval of 18 months, showed a statistically significant 16% reduction in breast cancer mortality 10 to 14 years after the initiation of screening [19]. We therefore assumed that a 16% reduction in breast cancer mortality would be achieved with screening done every 18 months. This screening interval is consistent with the guidelines of organizations [2, 3] that recommend screening every 1 to 2 years for 40- to 49-year-old women. In sensitivity analyses, we calculated the cost-effectiveness of annual and biennial screening, assuming the same 16% reduction in breast cancer mortality among screened women. Utilities Because there are few data on the utility that women place on life after treatment of breast cancer or the utility placed on living with metastatic breast cancer, we did not include utilities in the base-case analysis. Data from a small Australian study [33] (which observed a utility of about 0.8 for life after treatment of breast cancer and a utility of about 0.3 for life with metastatic cancer) are included in a sensitivity analysis to determine the extent to which cost per year of life saved might differ from cost per quality-adjusted life-year saved. Costs We included three costs: the cost of screening mammographic examinations, the cost of evaluating abnormal mammograms, and the cost of treating breast cancer (Table 2). Additional details on derivations of costs are given in the Appendix. The cost of screening mammography was based on the average cost ($91) reported by the National Cancer Institute's National Survey of Mammography Facilities [34]. This cost was inflated to 1995 dollars ($106) by using the consumer price index for medical services. We assumed that women in whom breast cancer was diagnosed continued to undergo screening mammography of the opposite breast, at the same cost, after the initial diagnosis of breast cancer. Table 2. Information Used to Calculate Costs The cost of evaluating abnormal mammographic results was calculated as a weighted average of procedures that may follow abnormal mammograms. This cost was also inflated to 1995 dollars. The distribution and types of follow-up procedures were based on those reported by the National Cancer Institute's National Survey of Mammography Facilities [35]. A range of costs for each procedure was based on data from Medicare, Pennsylvania Blue Cross, Group Health Cooperative, and Kaiser Permanente (Brown M. Personal communication). The percentage of abnormal mammograms was based on the percentage seen with high-quality modern screening mammography (Table 2) [36]. Population-based data on the cancer stage at diagnosis in screened compared with nonscreened women are sparse. O