Dataset Information

The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model.

ABSTRACT:

Background

Mammography trials, which are the primary sources of evidence for screening benefit, were conducted decades ago. Whether advances in systemic therapies have rendered previously observed benefits of screening less significant is unknown.

Objective

To compare the outcomes of breast cancer screening trials had they been conducted using contemporary systemic treatments with outcomes of trials conducted with previously used treatments.

Design

Computer simulation model of 3 virtual screening trials with similar reductions in advanced-stage cancer cases but reflecting treatment patterns in 1975 (prechemotherapy era), 1999, or 2015 (treatment according to receptor status).

Data sources

Meta-analyses of screening and treatment trials; study of dissemination of primary systemic treatments; SEER (Surveillance, Epidemiology, and End Results) registry.

Target population

U.S. women aged 50 to 74 years.

Time horizon

10 and 25 years.

Perspective

Population.

Intervention

Mammography, chemotherapy, tamoxifen, aromatase inhibitors, and trastuzumab.

Outcome measures

Breast cancer mortality rate ratio (MRR) and absolute risk reduction (ARR) obtained by the difference in cumulative breast cancer mortality between control and screening groups.

Results of base-case analysis

At 10 years, screening in a 1975 trial yielded an MRR of 90% and an ARR of 5 deaths per 10,000 women. A 2015 screening trial yielded a 10-year MRR of 90% and an ARR of 3 deaths per 10,000 women.

Results of sensitivity analysis

Greater reductions in advanced-stage disease yielded a greater screening effect, but MRRs remained similar across trials. However, ARRs were consistently lower under contemporary treatments. When contemporary treatments were available only for early-stage cases, the MRR was 88%.

Limitation

Disease models simplify reality and cannot capture all breast cancer subtypes.

Conclusion

Advances in systemic therapies for breast cancer have not substantively reduced the relative benefits of screening but have likely reduced the absolute benefits because of their positive effect on breast cancer survival.

Primary funding source

University of Washington and National Cancer Institute.

SUBMITTER: Birnbaum J

PROVIDER: S-EPMC5356482 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model.

Birnbaum Jeanette J Gadi Vijayakrishna K VK Markowitz Elan E Etzioni Ruth R

Annals of internal medicine 20160112 4

<h4>Background</h4>Mammography trials, which are the primary sources of evidence for screening benefit, were conducted decades ago. Whether advances in systemic therapies have rendered previously observed benefits of screening less significant is unknown.<h4>Objective</h4>To compare the outcomes of breast cancer screening trials had they been conducted using contemporary systemic treatments with outcomes of trials conducted with previously used treatments.<h4>Design</h4>Computer simulation model ...[more]

PMID: 26756332

Similar Datasets

Project description:BackgroundLung cancer is made up of distinct subtypes, including non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Although overall mortality from lung cancer has been declining in the United States, little is known about mortality trends according to cancer subtype at the population level because death certificates do not record subtype information.MethodsUsing data from Surveillance, Epidemiology, and End Results (SEER) areas, we assessed lung-cancer mortality and linked deaths from lung cancer to incident cases in SEER cancer registries. This allowed us to evaluate population-level mortality trends attributed to specific subtypes (incidence-based mortality). We also evaluated lung-cancer incidence and survival according to cancer subtype, sex, and calendar year. Joinpoint software was used to assess changes in incidence and trends in incidence-based mortality.ResultsMortality from NSCLC decreased even faster than the incidence of this subtype, and this decrease was associated with a substantial improvement in survival over time that corresponded to the timing of approval of targeted therapy. Among men, incidence-based mortality from NSCLC decreased 6.3% annually from 2013 through 2016, whereas the incidence decreased 3.1% annually from 2008 through 2016. Corresponding lung cancer-specific survival improved from 26% among men with NSCLC that was diagnosed in 2001 to 35% among those in whom it was diagnosed in 2014. This improvement in survival was found across all races and ethnic groups. Similar patterns were found among women with NSCLC. In contrast, mortality from SCLC declined almost entirely as a result of declining incidence, with no improvement in survival. This result correlates with limited treatment advances for SCLC in the time frame we examined.ConclusionsPopulation-level mortality from NSCLC in the United States fell sharply from 2013 to 2016, and survival after diagnosis improved substantially. Our analysis suggests that a reduction in incidence along with treatment advances - particularly approvals for and use of targeted therapies - is likely to explain the reduction in mortality observed during this period.

Project description:BackgroundLow back pain (LBP) causes the highest morbidity burden globally. The purpose of the present study was to project and compare the impact of three strategies for reducing the population health burden of LBP: weight loss, ergonomic interventions, and an exercise program.MethodsWe have developed a microsimulation model of LBP in Canada using a new modeling platform called SimYouLate. The initial population was derived from Cycle 1 (2001) of the Canadian Community Health Survey (CCHS). We modeled an open population 20 years of age and older. Key variables included age, sex, education, body mass index (BMI), type of work, having back problems, pain level in persons with back problems, and exercise participation. The effects of interventions on the risk of LBP were obtained from the CCHS for the effect of BMI, the Global Burden of Disease Study for occupational risks, and a published meta-analysis for the effect of exercise. All interventions lasted from 2021 to 2040. The population health impact of the interventions was calculated as a difference in years lived with disability (YLDs) between the base-case scenario and each intervention scenario, and expressed as YLDs averted per intervention unit or a proportion (%) of total LBP-related YLDs.ResultsIn the base-case scenario, LBP in 2020 was responsible for 424,900 YLDs in Canada and the amount increased to 460,312 YLDs in 2040. The effects of the interventions were as follows: 27,993 (95% CI 23,373, 32,614) YLDs averted over 20 years per 0.1 unit change in log-transformed BMI (9.5% change in BMI) among individuals who were overweight and those with obesity, 19,416 (16,275, 22,557) YLDs per 1% reduction in the proportion of workers exposed to occupational risks, and 26,058 (22,455, 29,661) YLDs averted per 1% increase in the proportion of eligible patients with back problems participating in an exercise program.ConclusionsThe study provides new data on the relationship between three types of interventions and the resultant reductions in LBP burden in Canada. According to our model, each of the interventions studied could potentially result in a substantial reduction in LBP-related disability.

Project description:BackgroundPersons with a negative result on screening colonoscopy are recommended to repeat the procedure in 10 years.ObjectiveTo assess the effectiveness and costs of colonoscopy versus other rescreening strategies after an initial negative colonoscopy result.DesignMicrosimulation model.Data sourcesLiterature and data from the Surveillance, Epidemiology, and End Results program.Target populationPersons aged 50 years who had no adenomas or cancer detected on screening colonoscopy.Time horizonLifetime.PerspectiveSocietal.InterventionNo further screening or rescreening starting at age 60 years with colonoscopy every 10 years, annual highly sensitive guaiac fecal occult blood testing (HSFOBT), annual fecal immunochemical testing (FIT), or computed tomographic colonography (CTC) every 5 years.Outcome measuresLifetime cases of colorectal cancer, life expectancy, and lifetime costs per 1000 persons, assuming either perfect or imperfect adherence.Results of base-case analysisRescreening with any method substantially reduced the risk for colorectal cancer compared with no further screening (range, 7.7 to 12.6 lifetime cases per 1000 persons [perfect adherence] and 17.7 to 20.9 lifetime cases per 1000 persons [imperfect adherence] vs. 31.3 lifetime cases per 1000 persons with no further screening). In both adherence scenarios, the differences in life-years across rescreening strategies were small (range, 30 893 to 30 902 life-years per 1000 persons [perfect adherence] vs. 30 865 to 30 869 life-years per 1000 persons [imperfect adherence]). Rescreening with HSFOBT, FIT, or CTC had fewer complications and was less costly than continuing colonoscopy.Results of sensitivity analysisResults were sensitive to test-specific adherence rates.LimitationData on adherence to rescreening were limited.ConclusionCompared with the currently recommended strategy of continuing colonoscopy every 10 years after an initial negative examination, rescreening at age 60 years with annual HSFOBT, annual FIT, or CTC every 5 years provides approximately the same benefit in life-years with fewer complications at a lower cost. Therefore, it is reasonable to use other methods to rescreen persons with negative colonoscopy results.Primary funding sourceNational Cancer Institute.

Project description:BackgroundThe appropriate age range for breast cancer screening remains a matter of debate. We aimed to estimate the effect of mammographic screening at ages 40-48 years on breast cancer mortality.MethodsWe did a randomised, controlled trial involving 23 breast screening units across Great Britain. We randomly assigned women aged 39-41 years, using individual randomisation, stratified by general practice, in a 1:2 ratio, to yearly mammographic screening from the year of inclusion in the trial up to and including the calendar year that they reached age 48 years (intervention group), or to standard care of no screening until the invitation to their first National Health Service Breast Screening Programme (NHSBSP) screen at approximately age 50 years (control group). Women in the intervention group were recruited by postal invitation. Women in the control group were unaware of the study. The primary endpoint was mortality from breast cancers (with breast cancer coded as the underlying cause of death) diagnosed during the intervention period, before the participant's first NHSBSP screen. To study the timing of the mortality effect, we analysed the results in different follow-up periods. Women were included in the primary comparison regardless of compliance with randomisation status (intention-to-treat analysis). This Article reports on long-term follow-up analysis. The trial is registered with the ISRCTN registry, ISRCTN24647151.Findings160 921 women were recruited between Oct 14, 1990, and Sept 24, 1997. 53 883 women (33·5%) were randomly assigned to the intervention group and 106 953 (66·5%) to the control group. Between randomisation and Feb 28, 2017, women were followed up for a median of 22·8 years (IQR 21·8-24·0). We observed a significant reduction in breast cancer mortality at 10 years of follow-up, with 83 breast cancer deaths in the intervention group versus 219 in the control group (relative rate [RR] 0·75 [95% CI 0·58-0·97]; p=0·029). No significant reduction was observed thereafter, with 126 deaths versus 255 deaths occurring after more than 10 years of follow-up (RR 0·98 [0·79-1·22]; p=0·86).InterpretationYearly mammography before age 50 years, commencing at age 40 or 41 years, was associated with a relative reduction in breast cancer mortality, which was attenuated after 10 years, although the absolute reduction remained constant. Reducing the lower age limit for screening from 50 to 40 years could potentially reduce breast cancer mortality.FundingNational Institute for Health Research Health Technology Assessment programme.

Dataset Information

The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model.

Background

Objective

Design

Data sources

Target population

Time horizon

Perspective

Intervention

Outcome measures

Results of base-case analysis

Results of sensitivity analysis

Limitation

Conclusion

Primary funding source

Publications

The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets