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Benefits and Harms of Mammography Screening for Women With Down Syndrome: a Collaborative Modeling Study.

ABSTRACT: 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.

SUBMITTER: Alagoz O

PROVIDER: S-EPMC6848489 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Benefits and Harms of Mammography Screening for Women With Down Syndrome: a Collaborative Modeling Study.

Alagoz Oguzhan O Hajjar Ali A Chootipongchaivat Sarocha S van Ravesteyn Nicolien T NT Yeh Jennifer M JM Ergun Mehmet Ali MA de Koning Harry J HJ Chicoine Brian B Martin Barry B

Journal of general internal medicine 20190805 11

<h4>Background</h4>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.<h4>Objective</h4>To determine the benefits and harms of various mammography screening strategies for women with Down syndrome using collaborative simulation modeling.<h4>Design</h4>Two es ...[more]

PMID: 31385214

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Project description: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.

Project description:Timing of initiation of screening for breast cancer is controversial in the United States.To determine the threshold relative risk (RR) at which the harm-benefit ratio of screening women aged 40 to 49 years equals that of biennial screening for women aged 50 to 74 years.Comparative modeling study.Surveillance, Epidemiology, and End Results program, Breast Cancer Surveillance Consortium, and medical literature.A contemporary cohort of women eligible for routine screening.Lifetime.Societal.Mammography screening starting at age 40 versus 50 years with different screening methods (film, digital) and screening intervals (annual, biennial).life-years gained, breast cancer deaths averted; harms: false-positive mammography findings; harm-benefit ratios: false-positive findings/life-years gained, false-positive findings/deaths averted.Screening average-risk women aged 50 to 74 years biennially yields the same false-positive findings/life-years gained as biennial screening with digital mammography starting at age 40 years for women with a 2-fold increased risk above average (median threshold RR, 1.9 [range across models, 1.5 to 4.4]). The threshold RRs are higher for annual screening with digital mammography (median, 4.3 [range, 3.3 to 10]) and when false-positive findings/deaths averted is used as an outcome measure instead of false-positive findings/life-years gained. The harm-benefit ratio for film mammography is more favorable than for digital mammography because film has a lower false-positive rate.The threshold RRs changed slightly when a more comprehensive measure of harm was used and were relatively insensitive to lower adherence assumptions.Risk was assumed to influence onset of disease without influencing screening performance.Women aged 40 to 49 years with a 2-fold increased risk have similar harm-benefit ratios for biennial screening mammography as average-risk women aged 50 to 74 years. Threshold RRs required for favorable harm-benefit ratios vary by screening method, interval, and outcome measure.National Cancer Institute.

Project description:BackgroundThe CONSORT statement specifies the need for a balanced presentation of both benefits and harms of medical interventions in trial reports. However, invitations to screening and newspaper articles often emphasize benefits and downplay or omit harms, and it is known that scientific articles can be influenced by conflicts of interest. We wanted to determine if a similar imbalance occurs in scientific articles on mammography screening and if it is related to author affiliation.MethodsWe searched PubMed in April 2005 for articles on mammography screening that mentioned a benefit or a harm and that were published in 2004 in English. Data extraction was performed by three independent investigators, two unblinded and one blinded for article contents, and author names and affiliation, as appropriate. The extracted data were compared and discrepancies resolved by two investigators in a combined analysis. We defined three groups of authors: (1) authors in specialties unrelated to mammography screening, (2) authors in screening-affiliated specialties (radiology or breast cancer surgery) who were not working with screening, or authors funded by cancer charities, and (3) authors (at least one) working directly with mammography screening programmes. We used a data extraction sheet with 17 items described as important benefits and harms in the 2002 WHO/IARC-report on breast cancer screening.ResultsWe identified 854 articles, and 143 were eligible for the study. Most were original research. Benefits were mentioned more often than harms (96% vs 62%, P < 0.001). Fifty-five (38%) articles mentioned only benefits, whereas seven (5%) mentioned only harms (P < 0.001). Overdiagnosis was mentioned in 35 articles (24%), but was more often downplayed or rejected in articles that had authors working with screening, (6/15; 40%) compared with authors affiliated by specialty or funding (1/6; 17%), or authors unrelated with screening (1/14; 7%) (P = 0.03). Benefits in terms of reduced breast cancer mortality were mentioned in 109 (76%) articles, and was more often provided as a relative risk reduction than an absolute risk reduction, where quantified (45 articles (31%) versus 6 articles (3%) (P < 0.001)).ConclusionScientific articles tend to emphasize the major benefits of mammography screening over its major harms. This imbalance is related to the authors' affiliation.

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: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:BackgroundDecades of persuasive messages have reinforced the importance of traditional screening mammography at regular intervals. A potential new paradigm, risk-based screening, adjusts mammography frequency based on a woman's estimated breast cancer risk in order to maximize mortality reduction while minimizing false positives and overdiagnosis. Women's views of risk-based screening are unknown.ObjectiveTo explore women's views and personal acceptability of a potential risk-based mammography screening paradigm.DesignFour semi-structured focus group discussions about screening mammography and surveys before provision of information about risk-based screening. We analyzed coded focus group transcripts using a mixed deductive (content analysis) and inductive (grounded theory) approach.ParticipantsConvenience sample of 29 women (40-74 years old) with no personal history of breast cancer recruited by print and online media in New Hampshire and Vermont.ResultsTwenty-seven out of 29 women reported having undergone mammography screening. All participants were white and most were highly educated. Some women accepted the idea that early cancer detection with traditional screening was beneficial-although many also reported hearing inconsistent recommendations from clinicians and mixed messages from media reports about mammography. Some women were familiar with a risk-based screening paradigm (primarily related to cervical cancer, n = 8) and thought matching screening mammography frequency to personal risk made sense (n = 8). Personal acceptability of risk-based screening was mixed. Some believed risk-based screening could reduce the harms of false positives and overdiagnosis (n = 7). Others thought screening less often might result in missing a dangerous diagnosis (n = 14). Many (n = 18) expressed concerns about the feasibility of risk-based screening and questioned whether breast cancer risk estimates could be accurate. Some suspected that risk-based mammography was motivated by a desire to save money (n = 6).ConclusionSome women thought risk-based screening made sense. Willingness to abandon traditional screening for the new paradigm was mixed. Broad acceptability of risk-based screening will require clearer communication about its rationale and feasibility and consistent messages from the health care team.

Project description:Guidelines recommend individualizing screening mammography decisions for women aged 75 years and older. However, little pragmatic guidance is available to help counsel patients.To provide an evidence-based approach for individualizing decision-making about screening mammography in older women.We searched PubMed for English-language studies in peer-reviewed journals published from January 1, 1990, to February 1, 2014, to identify risk factors for late-life breast cancer in women aged 65 years and older and to quantify the benefits and harms of screening mammography for women aged 75 years and older.Age is the major risk factor for developing and dying from breast cancer. Breast cancer risk factors that reflect hormonal exposures in the distant past, such as age at first birth or age at menarche, are less predictive of late-life breast cancer than factors indicating recent hormonal exposures such as high bone mass or obesity. Randomized trials of the benefits of screening mammography did not include women older than 74 years. Thus it is not known if screening mammography benefits older women. Observational studies favor extending screening mammography to older women who have a life expectancy of more than 10 years. Modeling studies estimate 2 fewer breast cancer deaths/1000 women who in their 70s continue biennial screening for 10 years instead of stopping screening at age 69. Potential harms of continued screening over 10 years include false-positive mammograms in approximately 200/1000 women screened and overdiagnosis (ie, finding breast cancer that would not have clinically surfaced otherwise) in approximately 13/1000 women screened. Providing information about life expectancy along with potential benefits and harms of screening may help older women's decision-making about screening mammography.For women with less than a 10-year life expectancy, recommendations to stop screening mammography should emphasize increased potential harms from screening and highlight health promotion measures likely to be beneficial over the short term. For women with a life expectancy of more than 10 years, deciding whether potential benefits of screening outweigh harms becomes a value judgment for patients, requiring a realistic understanding of screening outcomes.

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.

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Benefits and Harms of Mammography Screening for Women With Down Syndrome: a Collaborative Modeling Study.

Publications

Benefits and Harms of Mammography Screening for Women With Down Syndrome: a Collaborative Modeling Study.

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