This study is the first to comprehensively evaluate the cost-effectiveness of the combined use of MM with CBE in breast cancer early detection while accounting for costs of screening, work-up, biopsies due to true or false-positive examinations, and treatments. We assessed current recommended guidelines from three major cancer organizations and compared them with other realistic strategies that combine MM and CBE with different starting ages and intervals.
Compared to the alternatives, two of the recommended strategies are cost-effective in general: the NCI/USPSTF recommendation of annual MM and CBE from ages 40-79, and the most effective but expensive recommendation from the ACS that begins CBE at age 20, followed by MM and CBE from ages 40-79. The NCI/USPSTF recommendation of annual MM alone from ages 40 to 79 is cost-effective when the sensitivity of CBE is low, according to community-based settings. The NCI/USPSTF guideline of MM with CBE every two years was not an efficient strategy. A more cost-effective alternative is to provide MM and CBE in alternating years, which leads to more savings in QALYs with similar costs. Alternating exam years allows for annual examinations with one of the two screening modalities.
The strategy recommended by the ACS was the most expensive and effective. If society is willing to pay the required costs to save an additional QALY, this strategy is favorable. Alternatively, the cheapest but also effective alternative would be to offer biennial MM and CBE alternatively from ages 40-79 (strategy A).
Among all the strategies, only strategy A fell under a commonly accepted cost-effectiveness threshold of $50,000/QALY[53
]. Although this strategy is not as life saving as some other alternatives, the incremental gains in QALYs for the other efficient strategies D, F, I, and J, are not very large in comparison (1.8, 2.8, 3.1, or 3.6 days), with extra costs of $400, $900, $1,200, or $6,700 compared to strategy A. Compared to A, strategy J costs over $680,000 for an added QALY. The large cost difference is explained by the early accumulation of costs and discounting beginning at age 20. Under realistic monetary constraints, we must consider this large added expense when cheaper but still effective strategies exist. This issue is debatable for ethical reasons and depends on how much society is willing to pay to save an additional year of quality-adjusted life.
Our model does not make any assumptions on the effectiveness of CBE on mortality reduction, but relies on estimates of its sensitivity and specificity. The role of CBE in combination with MM depends on these estimates. The sensitivity analyses showed that higher specificity for CBE leads to lower patient recall rates, which decreases unnecessary work-ups and biopsies. However, the lower sensitivity of CBE increases the false-negative rate and delays diagnosis. The performance of screening exams affects the timing of diagnosis, recall rate, and intensity of treatment, which all affect overall costs and survival. The choice of survival model also has significant impact on the results. In a survival model where small changes in tumor size or nodal status have little effect on survival, differences in years gained due to screening may be small. Regardless of these changes in model assumptions, only three strategies remained more effective for a lower cost per QALY saved compared to the alternatives: 1) A: biennial MM and CBE in alternating years from ages 40-79, 2) I: annual MM and CBE from ages 40-79, and 3) J: the most expensive strategy of screening beginning at age 20.
Our analysis includes both direct costs of screening and treatment, and indirect costs for lost wages for women who die prematurely of breast cancer. Although it may be contended that the inclusion of lost wages in such an analysis as this may result in the double-counting of losses, we argue that our quality-of-life adjustments are due to treatment only. Adjustments beyond the duration of treatment are minimal and thus may not fully account for wages that may be lost due to early death from breast cancer.
There are several limitations to our study. First, we considered average medical costs as constants and did not take into account the variation across institutions. However, we believe our cost inputs are sufficient for this comparative analysis. Second, the surgery pattern used may not represent the general population. However, it has been shown that long-term costs for mastectomy and BCS are not notably different[42
]. Third, the treatment options do not include recent changes such as third-generation endocrine therapies and axillary or sentinel lymph node dissection, because these treatment patterns for the general population were not available in the literature. Other treatment options may be included in a future analysis.
While we considered quality-of-life adjustments due to treatments, our analysis did not account for physical and emotional effects of screening, unnecessary work-ups, or biopsies. It is difficult to assign monetary values to such effects. Finally, our simulation model assumed full compliance of participants in a screening and treatment plan, which allowed us to evaluate the potential effectiveness of a screening program.
In summary, several alternative cost-effective strategies were found to be more efficient than the recommended guidelines, or to have lower costs with minimal loss of benefit. In place of current recommendations, biennial MM and CBE in alternating years from ages 40-79 was the cheapest cost-effective alternative. If enough funds are available to add annual CBEs to a screening program, the next cost-effective alternative is to offer biennial MM and annual CBE from ages 40-79. Breast cancer screening strategies with lower costs and benefits comparable to those currently recommended should be considered for implementation in practice and for future guidelines.