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Collaborative Modeling of the Benefits and Harms Associated With Different U.S. Breast Cancer Screening Strategies.

ABSTRACT: BACKGROUND:Controversy persists about optimal mammography screening strategies. OBJECTIVE:To evaluate screening outcomes, taking into account advances in mammography and treatment of breast cancer. DESIGN:Collaboration of 6 simulation models using national data on incidence, digital mammography performance, treatment effects, and other-cause mortality. SETTING:United States. PATIENTS:Average-risk U.S. female population and subgroups with varying risk, breast density, or comorbidity. INTERVENTION:Eight strategies differing by age at which screening starts (40, 45, or 50 years) and screening interval (annual, biennial, and hybrid [annual for women in their 40s and biennial thereafter]). All strategies assumed 100% adherence and stopped at age 74 years. MEASUREMENTS:Benefits (breast cancer-specific mortality reduction, breast cancer deaths averted, life-years, and quality-adjusted life-years); number of mammograms used; harms (false-positive results, benign biopsies, and overdiagnosis); and ratios of harms (or use) and benefits (efficiency) per 1000 screens. RESULTS:Biennial strategies were consistently the most efficient for average-risk women. Biennial screening from age 50 to 74 years avoided a median of 7 breast cancer deaths versus no screening; annual screening from age 40 to 74 years avoided an additional 3 deaths, but yielded 1988 more false-positive results and 11 more overdiagnoses per 1000 women screened. Annual screening from age 50 to 74 years was inefficient (similar benefits, but more harms than other strategies). For groups with a 2- to 4-fold increased risk, annual screening from age 40 years had similar harms and benefits as screening average-risk women biennially from 50 to 74 years. For groups with moderate or severe comorbidity, screening could stop at age 66 to 68 years. LIMITATION:Other imaging technologies, polygenic risk, and nonadherence were not considered. CONCLUSION:Biennial screening for breast cancer is efficient for average-risk populations. Decisions about starting ages and intervals will depend on population characteristics and the decision makers' weight given to the harms and benefits of screening. PRIMARY FUNDING SOURCE:National Institutes of Health.

SUBMITTER: Mandelblatt JS

PROVIDER: S-EPMC5079106 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Collaborative Modeling of the Benefits and Harms Associated With Different U.S. Breast Cancer Screening Strategies.

Mandelblatt Jeanne S JS Stout Natasha K NK Schechter Clyde B CB van den Broek Jeroen J JJ Miglioretti Diana L DL Krapcho Martin M Trentham-Dietz Amy A Munoz Diego D Lee Sandra J SJ Berry Donald A DA van Ravesteyn Nicolien T NT Alagoz Oguzhan O Kerlikowske Karla K Tosteson Anna N A AN Near Aimee M AM Hoeffken Amanda A Chang Yaojen Y Heijnsdijk Eveline A EA Chisholm Gary G Huang Xuelin X Huang Hui H Ergun Mehmet Ali MA Gangnon Ronald R Sprague Brian L BL Plevritis Sylvia S Feuer Eric E de Koning Harry J HJ Cronin Kathleen A KA

Annals of internal medicine 20160112 4

<h4>Background</h4>Controversy persists about optimal mammography screening strategies.<h4>Objective</h4>To evaluate screening outcomes, taking into account advances in mammography and treatment of breast cancer.<h4>Design</h4>Collaboration of 6 simulation models using national data on incidence, digital mammography performance, treatment effects, and other-cause mortality.<h4>Setting</h4>United States.<h4>Patients</h4>Average-risk U.S. female population and subgroups with varying risk, breast d ...[more]

PMID: 26756606

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Project description:BACKGROUND:Women with Down syndrome have a lower breast cancer risk and significantly lower life expectancies than women without Down syndrome. Therefore, it is not clear whether mammography screening strategies used for women without Down syndrome would benefit women with Down syndrome in the same way. OBJECTIVE:To determine the benefits and harms of various mammography screening strategies for women with Down syndrome using collaborative simulation modeling. DESIGN:Two established Cancer Intervention and Surveillance Modeling Network (CISNET) simulation models estimated the benefits and harms of various screening strategies for women with Down syndrome over a lifetime horizon. PARTICIPANTS:We modeled a hypothetical cohort of US women with Down syndrome who were born in 1970. INTERVENTIONS:Annual, biennial, triennial, and one-time digital mammography screenings during the ages 40-74. MAIN MEASURES:The models estimated numbers of mammograms, false-positives, benign biopsies, breast cancer deaths prevented, and life-years gained per 1000 screened women when compared with no screening. KEY RESULTS:In average-risk women 50-74, biennial screening incurred 122 mammograms, 10 false-positive mammograms, and 1.4 benign biopsies per one life-year gained compared with no screening. In women with Down syndrome, the same screening strategy incurred 2752 mammograms, 242 false-positive mammograms, and 34 benign biopsies per one life-year gained compared with no screening. The harm/benefit ratio varied for other screening strategies, and was most favorable for one-time screening at age 50, which incurred 1629 mammograms, 144 false-positive mammograms, and 20 benign biopsies per one life-year gained compared with no screening. CONCLUSIONS:The harm/benefit ratios for various mammography screening strategies in women with Down syndrome are not as favorable as those for average-risk women. The benefit of screening mammography for women with Down syndrome is less pronounced due to lower breast cancer risk and shorter life expectancy.

Project description:BackgroundThe optimum screening policy for lung cancer is unknown.ObjectiveTo identify efficient computed tomography (CT) screening scenarios in which relatively more lung cancer deaths are averted for fewer CT screening examinations.DesignComparative modeling study using 5 independent models.Data sourcesThe National Lung Screening Trial; the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial; the Surveillance, Epidemiology, and End Results program; and the U.S. Smoking History Generator.Target populationU.S. cohort born in 1950.Time horizonCohort followed from ages 45 to 90 years.PerspectiveSocietal.Intervention576 scenarios with varying eligibility criteria (age, pack-years of smoking, years since quitting) and screening intervals.Outcome measuresBenefits included lung cancer deaths averted or life-years gained. Harms included CT examinations, false-positive results (including those obtained from biopsy/surgery), overdiagnosed cases, and radiation-related deaths.Results of best-case scenarioThe most advantageous strategy was annual screening from ages 55 through 80 years for ever-smokers with a smoking history of at least 30 pack-years and ex-smokers with less than 15 years since quitting. It would lead to 50% (model ranges, 45% to 54%) of cases of cancer being detected at an early stage (stage I/II), 575 screening examinations per lung cancer death averted, a 14% (range, 8.2% to 23.5%) reduction in lung cancer mortality, 497 lung cancer deaths averted, and 5250 life-years gained per the 100,000-member cohort. Harms would include 67,550 false-positive test results, 910 biopsies or surgeries for benign lesions, and 190 overdiagnosed cases of cancer (3.7% of all cases of lung cancer [model ranges, 1.4% to 8.3%]).Results of sensitivity analysisThe number of cancer deaths averted for the scenario varied across models between 177 and 862; the number of overdiagnosed cases of cancer varied between 72 and 426.LimitationsScenarios assumed 100% screening adherence. Data derived from trials with short duration were extrapolated to lifetime follow-up.ConclusionAnnual CT screening for lung cancer has a favorable benefit-harm ratio for individuals aged 55 through 80 years with 30 or more pack-years' exposure to smoking.Primary funding sourceNational Cancer Institute.

Project description:ImportanceThe US Preventive Services Task Force (USPSTF) is updating its 2008 colorectal cancer (CRC) screening recommendations.ObjectiveTo inform the USPSTF by modeling the benefits, burden, and harms of CRC screening strategies; estimating the optimal ages to begin and end screening; and identifying a set of model-recommendable strategies that provide similar life-years gained (LYG) and a comparable balance between LYG and screening burden.Design, setting, and participantsComparative modeling with 3 microsimulation models of a hypothetical cohort of previously unscreened US 40-year-olds with no prior CRC diagnosis.ExposuresScreening with sensitive guaiac-based fecal occult blood testing, fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy with or without stool testing, computed tomographic colonography (CTC), or colonoscopy starting at age 45, 50, or 55 years and ending at age 75, 80, or 85 years. Screening intervals varied by modality. Full adherence for all strategies was assumed.Main outcomes and measuresLife-years gained compared with no screening (benefit), lifetime number of colonoscopies required (burden), lifetime number of colonoscopy complications (harms), and ratios of incremental burden and benefit (efficiency ratios) per 1000 40-year-olds.ResultsThe screening strategies provided LYG in the range of 152 to 313 per 1000 40-year-olds. Lifetime colonoscopy burden per 1000 persons ranged from fewer than 900 (FIT every 3 years from ages 55-75 years) to more than 7500 (colonoscopy screening every 5 years from ages 45-85 years). Harm from screening was at most 23 complications per 1000 persons screened. Strategies with screening beginning at age 50 years generally provided more LYG as well as more additional LYG per additional colonoscopy than strategies with screening beginning at age 55 years. There were limited empirical data to support a start age of 45 years. For persons adequately screened up to age 75 years, additional screening yielded small increases in LYG relative to the increase in colonoscopy burden. With screening from ages 50 to 75 years, 4 strategies yielded a comparable balance of screening burden and similar LYG (median LYG per 1000 across the models): colonoscopy every 10 years (270 LYG); sigmoidoscopy every 10 years with annual FIT (256 LYG); CTC every 5 years (248 LYG); and annual FIT (244 LYG).Conclusions and relevanceIn this microsimulation modeling study of a previously unscreened population undergoing CRC screening that assumed 100% adherence, the strategies of colonoscopy every 10 years, annual FIT, sigmoidoscopy every 10 years with annual FIT, and CTC every 5 years performed from ages 50 through 75 years provided similar LYG and a comparable balance of benefit and screening burden.

Project description:BackgroundSurveillance with annual mammography and breast magnetic resonance imaging (MRI) is recommended for female survivors of childhood cancer treated with chest radiation, yet benefits, harms, and costs are uncertain.ObjectiveTo compare the benefits, harms, and cost-effectiveness of breast cancer screening strategies in childhood cancer survivors.DesignCollaborative simulation modeling using 2 Cancer Intervention and Surveillance Modeling Network breast cancer models.Data sourcesChildhood Cancer Survivor Study and published data.Target populationWomen aged 20 years with a history of chest radiotherapy.Time horizonLifetime.PerspectivePayer.InterventionAnnual MRI with or without mammography, starting at age 25, 30, or 35 years.Outcome measuresBreast cancer deaths averted, false-positive screening results, benign biopsy results, and incremental cost-effectiveness ratios (ICERs).Results of base-case analysisLifetime breast cancer mortality risk without screening was 10% to 11% across models. Compared with no screening, starting at age 25 years, annual mammography with MRI averted the most deaths (56% to 71%) and annual MRI (without mammography) averted 56% to 62%. Both strategies had the most screening tests, false-positive screening results, and benign biopsy results. For an ICER threshold of less than $100 000 per quality-adjusted life-year gained, screening beginning at age 30 years was preferred.Results of sensitivity analysisAssuming lower screening performance, the benefit of adding mammography to MRI increased in both models, although the conclusions about preferred starting age remained unchanged.LimitationElevated breast cancer risk was based on survivors diagnosed with childhood cancer between 1970 and 1986.ConclusionEarly initiation (at ages 25 to 30 years) of annual breast cancer screening with MRI, with or without mammography, might reduce breast cancer mortality by half or more in survivors of childhood cancer.Primary funding sourceAmerican Cancer Society and National Institutes of Health.

Project description:BackgroundCancer screening should be recommended only when the balance between benefits and harms is favorable. This review evaluated how U.S. cancer screening guidelines reported harms, within and across organ-specific processes to screen for cancer.ObjectiveTo describe current reporting practices and identify opportunities for improvement.DesignReview of guidelines.SettingUnited States.PatientsPatients eligible for screening for breast, cervical, colorectal, lung, or prostate cancer according to U.S. guidelines.MeasurementsInformation was abstracted on reporting of patient-level harms associated with screening, diagnostic follow-up, and treatment. The authors classified harms reporting as not mentioned, conceptual, qualitative, or quantitative and noted whether literature was cited when harms were described. Frequency of harms reporting was summarized by organ type.ResultsHarms reporting was inconsistent across organ types and at each step of the cancer screening process. Guidelines did not report all harms for any specific organ type or for any category of harm across organ types. The most complete harms reporting was for prostate cancer screening guidelines and the least complete for colorectal cancer screening guidelines. Conceptualization of harms and use of quantitative evidence also differed by organ type.LimitationsThis review considers only patient-level harms. The authors did not verify accuracy of harms information presented in the guidelines.ConclusionThe review identified opportunities for improving conceptualization, assessment, and reporting of screening process-related harms in guidelines. Future work should consider nuances associated with each organ-specific process to screen for cancer, including which harms are most salient and where evidence gaps exist, and explicitly explore how to optimally weigh available evidence in determining net screening benefit. Improved harms reporting could aid informed decision making, ultimately improving cancer screening delivery.Primary funding sourceNational Cancer Institute.

Project description:The U.S. Preventive Services Task Force recently concluded that the harms of existing prostate-specific antigen (PSA) screening strategies outweigh the benefits.To evaluate comparative effectiveness of alternative PSA screening strategies.Microsimulation model of prostate cancer incidence and mortality quantifying harms and lives saved for alternative PSA screening strategies.National and trial data on PSA growth, screening and biopsy patterns, incidence, treatment distributions, treatment efficacy, and mortality.A contemporary cohort of U.S. men.Lifetime.Societal.35 screening strategies that vary by start and stop ages, screening intervals, and thresholds for biopsy referral.PSA tests, false-positive test results, cancer detected, overdiagnoses, prostate cancer deaths, lives saved, and months of life saved.Without screening, the risk for prostate cancer death is 2.86%. A reference strategy that screens men aged 50 to 74 years annually with a PSA threshold for biopsy referral of 4 µg/L reduces the risk for prostate cancer death to 2.15%, with risk for overdiagnosis of 3.3%. A strategy that uses higher PSA thresholds for biopsy referral in older men achieves a similar risk for prostate cancer death (2.23%) but reduces the risk for overdiagnosis to 2.3%. A strategy that screens biennially with longer screening intervals for men with low PSA levels achieves similar risks for prostate cancer death (2.27%) and overdiagnosis (2.4%), but reduces total tests by 59% and false-positive results by 50%.Varying incidence inputs or reducing the survival improvement due to screening did not change conclusions.The model is a simplification of the natural history of prostate cancer, and improvement in survival due to screening is uncertain.Compared with standard screening, PSA screening strategies that use higher thresholds for biopsy referral for older men and that screen men with low PSA levels less frequently can reduce harms while preserving lives.National Cancer Institute and Centers for Disease Control and Prevention.

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Collaborative Modeling of the Benefits and Harms Associated With Different U.S. Breast Cancer Screening Strategies.

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Collaborative Modeling of the Benefits and Harms Associated With Different U.S. Breast Cancer Screening Strategies.

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