Among Medicare enrollees, CAD use during screening mammography is associated with increased incidence of DCIS and no difference in the incidence of invasive cancer. It is, however, associated with greater likelihood that incident invasive cancer will be early- rather than late-stage and rates of diagnostic testing among women without breast cancer will be greater.
Weighing the potential benefits and harms of CAD use is complex, particularly because mortality benefits of screening interventions likely require many years to emerge (4
). Indeed, mortality benefits in randomized trials of breast cancer screening are probably attributable to favorable shifts in invasive breast cancer stage that evolved during several rounds of screening over many years (19
). Thus, it is difficult to conceive that a favorable stage shift could emerge during the 1-year period after mammography in this study. Moreover, secondary analyses do not suggest that CAD was associated with earlier diagnosis of invasive breast cancer during the follow-up, as would be expected if the observed differences in early- and late-stage cancer incidence were attributable to enhanced sensitivity for earlier-stage cancer with CAD. On the other hand, secondary analyses do not suggest that the observed differences in late-stage cancer incidence are due to reduced sensitivity for late-stage cancer with CAD. Longer-term studies of the association of CAD with cancer stage are warranted to elucidate its clinical effect on invasive breast cancer stage.
Computer-aided detection was consistently associated with greater detection of DCIS in primary and secondary analyses. Treatment of DCIS detected by CAD may prevent progression to lethal invasive breast cancer and may avert more extensive treatment of subsequent invasive cancer. On the other hand, recent estimates suggest that 1 in 4 screen-detected invasive breast cancer cases are detected and treated in women who would have died of other causes without screening (33
). The potential for overtreatment may be greater with DCIS (a noninvasive precursor of invasive cancer), particularly among an elderly population with more limited life expectancy than a younger screening population (34
Among women without breast cancer, CAD use was associated with increased diagnostic testing after screening, especially with diagnostic mammography but also with breast ultrasonography and biopsy. These findings are consistent with previous research demonstrating associations between CAD use and increased false-positive rates of screening mammography (5
). Diagnostic testing after false-positive mammography is associated with patient anxiety and accounts for a substantial part of the total costs of mammography screening (3
). In post hoc, subgroup analyses, associations between CAD and increased diagnostic testing were greater among women with previous non-CAD mammography and during concurrent digital mammography. It is possible that CAD particularly reduces screening specificity during its first application on an individual woman or on a woman’s first digital mammogram.
Within a study of 90 BCSC (Breast Cancer Surveillance Consortium) facilities, CAD use was not associated with more favorable stage, size, or lymph node status of invasive breast cancer (16
). Differences in study samples and designs may explain the contrasting results of the BCSC analysis and the current study. First, the BCSC analysis included a smaller breast cancer sample (7722 participants vs. 46 361 in the current study), so it may have been underpowered to detect favorable associations between CAD and breast cancer stage, size, or lymph node status. Second, the BCSC analysis assessed CAD use at the facility level, potentially leading to misclassification of CAD status of individual mammography and attenuation of differences in outcomes by CAD use. On the other hand, unlike the BCSC analyses, the present study lacked measures of breast density and hormone therapy, although our adjustment for study year addresses to some extent the decline in use of hormone therapy since 2002 (37
In the United States, the SEER–Medicare data may be unique in their ability to couple mammography data from claims with cancer outcome data for such a large sample of women with incident breast cancer. However, these data do not specifically address the effect of CAD during screening among women younger than 65 years. In addition, evidence for screening mammography effectiveness among women older than 75 years is limited (19
). However, in analyses stratified by patient age 67 to 75 years versus 75 to 89 years, associations between CAD and outcomes were generally consistent with main analyses ( and , available at www.annals.org
Appendix Table 8
Breast Cancer Incidence Rates by CAD Use, Stratified by Patient Age*
Residual confounding by unmeasured factors other than CAD may influence results. However, secondary analyses suggest that previous mammography exposure, confounding by unmeasured breast density, or unmeasured radiologist characteristics are not likely to explain the observed differences (Appendix
). Our analysis is also limited by the absence of information on mammogram interpretation, so we could not assess important performance measures, such as sensitivity or specificity. Results may not be generalizable to Medicare beneficiaries enrolled in managed care plans. Results may also reflect a transitional period when many radiologists were learning to use CAD (38
). Statistically significant associations may be attributable to chance, particularly in post hoc subgroup analyses.
In conclusion, CAD use among older U.S. women having screening mammography is associated with increased diagnosis of DCIS and the diagnosis of invasive breast cancer at earlier stage. However, CAD use is also associated with increased diagnostic testing among women without breast cancer. The long-term effect of CAD on breast cancer stage, mortality, quality of life, and costs warrants investigation.