Dataset Information

The Value of All-Cause Mortality as a Metric for Assessing Breast Cancer Screening.

ABSTRACT: Although screening mammography has been demonstrated to contribute to reducing mortality due to breast cancer, some have suggested that reduced all-cause mortality should constitute the burden of proof for effectiveness. Using a microsimulation model of the development, detection, and treatment of breast cancer, it is straightforward to demonstrate that this is an unrealistic expectation for trials of practical size and period of observation, even where the reduction of breast cancer mortality is substantial. Estimates of all-cause mortality will depend not only on the efficacy of the screening intervention but also on the alignment between the age distribution of the effect of screening on reduction of deaths and that of the other major causes of death. The size of a randomized trial required to demonstrate a reduction in all-cause mortality will, therefore, depend on the length and timing of the observation period and will typically be at least 10 times larger than the size of a trial powered to test for a reduction in deaths due to breast cancer. For breast cancer, which represents a small fraction of overall deaths, all-cause mortality is neither a practical nor informative metric for assessing the effectiveness of screening.

SUBMITTER: Yaffe MJ

PROVIDER: S-EPMC7566389 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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The Value of All-Cause Mortality as a Metric for Assessing Breast Cancer Screening.

Yaffe Martin J MJ Mainprize James G JG

Journal of the National Cancer Institute 20201001 10

Although screening mammography has been demonstrated to contribute to reducing mortality due to breast cancer, some have suggested that reduced all-cause mortality should constitute the burden of proof for effectiveness. Using a microsimulation model of the development, detection, and treatment of breast cancer, it is straightforward to demonstrate that this is an unrealistic expectation for trials of practical size and period of observation, even where the reduction of breast cancer mortality i ...[more]

PMID: 32058543

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Project description:ObjectiveTo evaluate the effectiveness of contemporary mammography screening using individual information about screening history and breast cancer mortality from public screening programmes.DesignProspective cohort study of Norwegian women who were followed between 1986 and 2009. Within that period (1995-2005), a national mammography screening programme was gradually implemented, with biennial invitations sent to women aged 50-69 years.ParticipantsAll Norwegian women aged 50-79 between 1986 and 2009.Main outcome measuresMultiple Poisson regression analysis was used to estimate breast cancer mortality rate ratios comparing women who were invited to screening (intention to screen) with women who were not invited, with a clear distinction between cases of breast cancer diagnosed before (without potential for screening effect) and after (with potential for screening effect) the first invitation for screening. We took competing causes of death into account by censoring women from further follow-up who died from other causes. Based on the observed mortality reduction combined with the all cause and breast cancer specific mortality in Norway in 2009, we used the CISNET (Cancer Intervention and Surveillance Modeling Network) Stanford simulation model to estimate how many women would need to be invited to biennial mammography screening in the age group 50-69 years to prevent one breast cancer death during their lifetime.ResultsDuring 15 193 034 person years of observation (1986-2009), deaths from breast cancer occurred in 1175 women with a diagnosis after being invited to screening and 8996 women who had not been invited before diagnosis. After adjustment for age, birth cohort, county of residence, and national trends in deaths from breast cancer, the mortality rate ratio associated with being invited to mammography screening was 0.72 (95% confidence interval 0.64 to 0.79). To prevent one death from breast cancer, 368 (95% confidence interval 266 to 508) women would need to be invited to screening.ConclusionInvitation to modern mammography screening may reduce deaths from breast cancer by about 28%.

Project description:ImportanceGuidelines recommend against routine breast and prostate cancer screenings in older adults with less than 10 years' life expectancy. One study using a claims-based prognostic index showed that receipt of cancer screening itself was associated with lower mortality, suggesting that the index may misclassify individuals when used to inform cancer screening, but this finding was attributed to residual confounding because the index did not account for functional status.ObjectiveTo examine whether cancer screening remains significantly associated with all-cause mortality in older adults after accounting for both comorbidities and functional status.Design, setting, and participantsThis cohort study included individuals older than 65 years who were eligible for breast or prostate cancer screening and who participated in the 2004 Health and Retirement Study. Data were linked to Medicare claims from 2001 to 2015. Data analysis was conducted from January to November 2020.Main outcomes and measuresA Cox model was used to estimate the association between all-cause mortality over 10 years and receipt of screening mammogram or prostate-specific antigen (PSA) test, adjusting for variables in a prognostic index that included age, sex, comorbidities, and functional status. Potential confounders (ie, education, income, marital status, geographic region, cognition, self-reported health, self-care, and self-perceived mortality risk) of the association between cancer screening and mortality were also tested.ResultsThe breast cancer screening cohort included 3257 women (mean [SD] age, 77.8 [7.5] years); the prostate cancer screening cohort included 2085 men (mean [SD] age, 76.1 [6.8] years). Receipt of screening mammogram was associated with lower hazard of all-cause mortality after accounting for all index variables (adjusted hazard ratio [aHR], 0.67; 95% CI, 0.60-0.74). A weaker, but still statistically significant, association was found for screening PSA (aHR 0.88; 95% CI, 0.78-0.99). None of the potential confounders attenuated the association between screening and mortality except for cognition, which attenuated the aHR for mammogram from 0.67 (95% CI, 0.60-0.74) to 0.73 (95% CI, 0.64-0.82) and the aHR for PSA from 0.88 (95% CI, 0.78-0.99) to 0.92 (95% CI, 0.80-1.05), making PSA screening no longer statistically significant.Conclusions and relevanceIn this study, cognition attenuated the observed association between cancer screening and mortality among older adults. These findings suggest that existing mortality prediction algorithms may be missing important variables that are associated with receipt of cancer screening and long-term mortality. Relying solely on algorithms to determine cancer screening may misclassify individuals as having limited life expectancy and stop screening prematurely. Screening decisions need to be individualized and not solely dependent on life expectancy prediction.

Dataset Information

The Value of All-Cause Mortality as a Metric for Assessing Breast Cancer Screening.

Publications

The Value of All-Cause Mortality as a Metric for Assessing Breast Cancer Screening.

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