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P36: How to Study the Effect of the Duration of Treatment Using Real-World Data: A Case Study Using Breast Cancer Screening

Poster Presenter

Xabier García De Albéniz

Director
Research Triangle Institute HS
Spain

Objectives

To emulate a target trial using real-world data to estimate the effect of continuing breast cancer screening for 8 years compared with stopping screening, on breast cancer mortality in Medicare beneficiaries aged 70 to 84 years who were regularly screened.

Method

We estimated the effect of continuing annual mammography vs stopping screening by emulating target trial to avoid immortal time bias. We estimated the eight-year breast cancer mortality, incidence, treatments, and positive predictive values. We included beneficiaries aged 70 to 84.

Results

A total of 2 639 194 individuals contributed 4 656 465 person-years to the “stop screening” strategy and 7 170 142 person-years to the “continue screening” strategy. In women aged 70 to 74 years, the estimated difference in 8-year risk for breast cancer death between continuing and stopping screening was -1.0 (95% CI, -2.3 to 0.1) death per 1000 women (hazard ratio, 0.78 [CI, 0.63 to 0.95]) (a negative risk difference favors continuing). In those aged 75 to 84 years, the corresponding risk difference was 0.07 (CI, -0.93 to 1.3) deaths per 1000 women (hazard ratio, 1.00 [CI, 0.83 to 1.19]). A secondary analysis using a causal framework in the presence of competing events estimated both the direct effect and the total effect of breast cancer screening on breast cancer mortality and the results did not differ from the main analysis. We used corpus uteri cancer mortality as a negative control outcome to assess the presence of unmeasured confounding and the association was null (the estimated difference in 8-year risk for corpus uteri cancer death between continuing and stopping breast cancer screening was 0.02 [95% CI, -0.28 to 0.23] death per 1000 women in women aged 70-74 and 0.10 [95% CI, -0.21 to 0.44] death per 1000 women in women aged 75-84 ). The estimated 8-year risk for breast cancer diagnosis was 5.5% with the “continue screening” strategy and 3.9% with the “stop screening” strategy. The positive predictive value of mammography done for any reason after baseline was 38.5% with the “continue screening” strategy and 45.3% with the “stop screening” strategy. Women diagnosed with breast cancer under the “stop screening” strategy (that is, those whose breast cancer was detected by means other than a screening mammogram) were more likely to receive chemotherapy but less likely to receive radiotherapy, lumpectomies, or any other type of surgery.

Conclusion

The most recent metanalysis of breast cancer screening found that the risk of breast cancer death associated with receiving screening for 10 years between ages 70 and 74 was -1.3 (95% CI, 10.7 to 31.7) breast cancer deaths per 1000 women (HR 0.80 [95% CI 0.51-1.28]). Our estimates reproduced these results in the same age group (8-year risk of breast cancer death was -1.0 [95% CI, -2.3 to 0.] death per 1000 women, hazard ratio: 0.78 [CI, 0.63 to 0.95]) and provided a more precise estimate by obtaining a narrower 95% CI. Unfortunately, none of the clinical trials included women older than 74 and therefore whether to continue screening beyond that age was an unanswered question. After replicating the estimates of clinical trials for age 70-74, we expanded the analysis to the 75-84 age group and found that continuing to screen women aged 75 years or older does not seem to affect 8-year breast cancer mortality. Our analysis of the total effect and the direct effect, which accounts for the presence of competing risk of death, were essentially the same as the main estimates. Therefore, the null effect in older age groups is unlikely to be because of the presence of competing causes of death. Previous observational studies of breast cancer screening in older women have been criticized for the presence of lead time and length time biases. Our real-world design mitigates these by emulating a target trial that explicitly aligns eligibility and assignment to screening strategies at baseline and adjusts for both baseline and postbaseline prognostic factors. In conclusion, continuing annual breast cancer screening past age 75 years did not result in substantial reductions in 8-year breast cancer mortality compared with stopping screening.