Systematic reviews as a 'lens of evidence': Determinants of benefits and harms of breast cancer screening.
ABSTRACT: This systematic review, stimulated by inconsistency in secondary evidence, reports the benefits and harms of breast cancer (BC) screening and their determinants according to systematic reviews. A systematic search, which identified 9,976 abstracts, led to the inclusion of 58 reviews. BC mortality reduction with screening mammography was 15-25% in trials and 28-56% in observational studies in all age groups, and the risk of stage III+ cancers was reduced for women older than 49 years. Overdiagnosis due to mammography was 1-60% in trials and 1-12% in studies with a low risk of bias, and cumulative false-positive rates were lower with biennial than annual screening (3-17% vs 0.01-41%). There is no consistency in the reviews' conclusions about the magnitude of BC mortality reduction among women younger than 50 years or older than 69 years, or determinants of benefits and harms of mammography, including the type of mammography (digital vs screen-film), the number of views and the screening interval. Similarly, there was no solid evidence on determinants of benefits and harms or BC mortality reduction with screening by ultrasonography or clinical breast examination (sensitivity ranges, 54-84% and 47-69%, respectively), and strong evidence of unfavourable benefit-to-harm ratio with breast self-examination. The reviews' conclusions were not dependent on the quality of the reviews or publication date. Systematic reviews on mammography screening, mainly from high-income countries, systematically disagree on the interpretation of the benefit-to-harm ratio. Future reviews are unlikely to clarify the discrepancies unless new original studies are published.
Project description:BACKGROUND:Debates about the benefits and harms of mammography continue despite the accumulation of evidence. We sought to quantify the disagreement across systematic reviews of mammography and determine whether author or design characteristics were associated with conclusions that were favourable to the use of mammography for routine breast cancer screening. METHODS:We identified systematic reviews of mammography published between January 2000 and November 2015, and extracted information about the selection of evidence, age groups, the use of meta-analysis, and authors' professions and financial competing interest disclosures. Conclusions about specific age groups were graded as favourable if they stated that there were meaningful benefits, that benefits of mammography outweighed harms, or that harms were inconsequential. The main outcome measures were the proportions of favourable conclusions relative to review design and author characteristics. RESULTS:From 59 conclusions identified in 50 reviews, 42% (25/59) were graded as favourable by two investigators. Among the conclusions produced by clinicians, 63% (12/19) were graded as favourable compared to 32% (13/40) from other authors. In the 50-69 age group where the largest proportion of systematic reviews were focused, conclusions drawn by authors without financial competing interests (odds ratio 0.06; 95% CI 0.07-0.56) and non-clinicians (odds ratio 0.11; 95% CI 0.01-0.84) were less likely to be graded as favourable. There was no trend in the proportion of favourable conclusions over the period, and we found no significant association between review design characteristics and favourable conclusions. CONCLUSIONS:Differences in the conclusions of systematic reviews of the evidence for mammography have persisted for 15 years. We found no strong evidence that design characteristics were associated with greater support for the benefits of mammography in routine breast cancer screening. Instead, the results suggested that the specific expertise and competing interests of the authors influenced the conclusions of systematic reviews.
Project description:<h4>Background</h4>Trans people face uncertain risk for breast cancer and barriers to accessing breast screening. Our objectives were to identify and synthesize primary research evidence on the effect of cross-sex hormones (CSHs) on breast cancer risk, prognosis and mortality among trans people, the benefits and harms of breast screening in this population, and existing clinical practice recommendations on breast screening for trans people.<h4>Methods</h4>We conducted 2 systematic reviews of primary research, 1 on the effect of CSHs on breast cancer risk, prognosis and mortality, and the other on the benefits and harms of breast screening, and a third systematic review of guidelines on existing screening recommendations for trans people. We searched PubMed, MEDLINE, Embase, CINAHL, the Cochrane Database of Systematic Reviews and grey literature sources for primary research, guidelines and position statements published in English between 1997 and 2017. Citations were screened by 2 independent reviewers. One reviewer extracted data and assessed methodological quality of included articles; a second reviewer verified these in full. The results were synthesized narratively.<h4>Results</h4>Four observational studies, 6 guidelines and 5 position statements were included. Observational evidence of very low certainty did not show an effect of CSHs on breast cancer risk in trans men or trans women. Among trans women, painfulness of mammography and ultrasonography was low. There was no evidence on the effect of CSHs on breast cancer prognosis and mortality, or on benefits and other harms of screening. Existing clinical practice documents recommended screening for distinct trans subpopulations; however, recommendations varied.<h4>Interpretation</h4>The limited evidence does not show an effect of CSHs on breast cancer risk. Although there is insufficient evidence to determine the potential benefits and harms of breast screening, existing clinical practice documents generally recommend screening for trans people; further large-scale prospective comparative research is needed.
Project description:<h4>Background</h4>The 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.<h4>Methods</h4>We 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.<h4>Results</h4>We 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)).<h4>Conclusion</h4>Scientific articles tend to emphasize the major benefits of mammography screening over its major harms. This imbalance is related to the authors' affiliation.
Project description:The main benefit of breast cancer (BC) screening is a reduction in mortality from BC. However, screening also causes harms such as overdiagnosis and false-positive results. The balance between benefits and harms varies by age. This study aims to assess how harm-to-benefit ratios of BC screening vary by age in the Netherlands, Finland, Italy and Slovenia. Using microsimulation models, we simulated biennial screening with 100% attendance at varying ages for cohorts of women followed over a lifetime. The number of overdiagnoses, false-positive diagnoses, BC deaths averted and life-years gained (LYG) were calculated per 1000 women. We compared four strategies (50-69, 45-69, 45-74 and 50-74) by calculating four harm-to-benefit ratios, respectively. Compared to the reference strategy 50-69, screening women at 45-74 or 50-74 years would be less beneficial in any of the four countries than screening women at 45-69, which would result in relatively fewer overdiagnoses per death averted or LYG. At the same time, false-positive results per death averted would increase substantially. Adapting the age range of BC screening is an option to improve harm-to-benefit ratios in all four countries. Prioritization of considered harms and benefits affects the interpretation of results.
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:BACKGROUND:The decision to participate or not in breast cancer screening is complex due to the trade-off between the expected benefit of breast cancer mortality reduction and the major harm of overdiagnosis. It seems ethically necessary to inform women so that they can actively participate in decision-making and make an informed choice based on their values and preferences. The objective of this study is to assess the effects of receiving information about the benefits and harms of screening on decision-making, in women approaching the age of invitation to mammography screening. METHODS:A two-stage, randomized controlled trial (RCT). In the first stage, 40 Basic Health Areas (BHAs) will be selected and randomized to intervention or control. In the second stage, women within each BHA will be randomly selected (n?=?400). Four breast cancer screening programs (BCSPs) of the Spanish public health system, three in Catalonia and one in the Canary Islands will participate in the study. Women in the intervention arm will receive a leaflet with detailed information on the benefits and harms of screening using mammography. Women in the control arm will receive a standard leaflet that does not mention harms and recommends accepting the invitation to participate in the biennial examinations of the BCSP. The primary outcome is informed choice, a dichotomous variable that combines knowledge, attitudes, and intentions. Secondary outcomes include decisional conflict; confidence in the decision made; anxiety about screening participation; worry about breast cancer; anticipated regret; time perspective; perceived importance of benefits/harms of screening; perceived risk of breast cancer; and leaflet acceptability. Primary and secondary outcomes are assessed 2-3 weeks after the intervention. DISCUSSION:This is the first RCT that assesses the effect of informing about the benefits and harms of breast cancer screening in Spain in women facing the decision to be screened using mammography. It aims to assess the impact of information on several decisional outcomes and to contribute to paving the road towards shared decision-making in breast cancer screening in our country. TRIAL REGISTRATION:ClinicalTrials.gov registry, ID: NCT03046004 . Retrospectively registered on 4 February 2017. Trial name: InforMa study.
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:<h4>Objective</h4>To assess the determinants of the participation rate in breast cancer screening programs by conducting a systematic review of reviews.<h4>Methods</h4>We conducted a systematic search in PubMed via Medline, Scopus, Embase, and Cochrane identifying the literature up to April 2019. Out of 2258 revealed unique abstracts, we included 31 reviews, from which 25 were considered as systematic. We applied the Walsh & McPhee Systems Model of Clinical Preventive Care to systematize the determinants of screening participation.<h4>Results</h4>The reviews, mainly in high-income settings, reported a wide range for breast cancer screening participation rate: 16-90%. The determinants of breast cancer screening participation were simple low-cost interventions such as invitation letters, basic information on screening, multiple reminders, fixed appointments, prompts from healthcare professionals, and healthcare organizational factors (e.g. close proximity to screening facility). More complex interventions (such as face-to-face counselling or home visits), mass media or improved access to transport should not be encouraged by policy makers unless other information appears. The repeated participation in mammography screening was consistently high, above 62%. Previous positive experience with screening influenced the repeated participation in screening programs. The reviews were inconsistent in the use of terminology related to breast cancer screening participation, which may have contributed to the heterogeneity in the reported outcomes.<h4>Conclusions</h4>This study shows that consistent findings of systematic reviews bring more certainty into the conclusions on the effects of simple invitation techniques, fixed appointments and prompts, as well as healthcare organizational factors on promoting participation rate in screening mammography.
Project description:<h4>Background</h4>This systematic review is an update of evidence since the 2002 U.S. Preventive Services Task Force recommendation on breast cancer screening.<h4>Purpose</h4>To determine the effectiveness of mammography screening in decreasing breast cancer mortality among average-risk women aged 40 to 49 years and 70 years or older, the effectiveness of clinical breast examination and breast self-examination, and the harms of screening.<h4>Data sources</h4>Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the fourth quarter of 2008), MEDLINE (January 2001 to December 2008), reference lists, and Web of Science searches for published studies and Breast Cancer Surveillance Consortium for screening mammography data.<h4>Study selection</h4>Randomized, controlled trials with breast cancer mortality outcomes for screening effectiveness, and studies of various designs and multiple data sources for harms.<h4>Data extraction</h4>Relevant data were abstracted, and study quality was rated by using established criteria.<h4>Data synthesis</h4>Mammography screening reduces breast cancer mortality by 15% for women aged 39 to 49 years (relative risk, 0.85 [95% credible interval, 0.75 to 0.96]; 8 trials). Data are lacking for women aged 70 years or older. Radiation exposure from mammography is low. Patient adverse experiences are common and transient and do not affect screening practices. Estimates of overdiagnosis vary from 1% to 10%. Younger women have more false-positive mammography results and additional imaging but fewer biopsies than older women. Trials of clinical breast examination are ongoing; trials for breast self-examination showed no reductions in mortality but increases in benign biopsy results.<h4>Limitation</h4>Studies of older women, digital mammography, and magnetic resonance imaging are lacking.<h4>Conclusion</h4>Mammography screening reduces breast cancer mortality for women aged 39 to 69 years; data are insufficient for older women. False-positive mammography results and additional imaging are common. No benefit has been shown for clinical breast examination or breast self-examination.
Project description:Systematic reviews with economic components are important decision tools for stakeholders seeking to evaluate technologies, such as breast cancer screening (BCS) programs. This overview of systematic reviews explores the determinants of the cost-effectiveness of BCS and assesses the quality of secondary evidence. The search identified 30 systematic reviews that reported on the determinants of the cost-effectiveness of BCS, including the costs of breast cancer and BCS. While the quality of the reviews varied widely, only four out of 30 papers were considered to be of a high quality. We did not identify publication bias in the original evidence on the cost-effectiveness of mammography screening; however, we highlight a need for improved clarity in both reporting and data verification. The reviews consisted mainly of studies from high-income countries. Breast cancer costs varied widely among the studies. Factors leading to higher costs included: time (diagnosis and last months before death), later stage or metastases, recurrence of the disease, age below 64 years and type of follow-up (more intensive or more specialized). Overall, screening with mammography was considered cost-effective in the age range 50-69 years in Western European and Northern American countries but not for older or younger women. Its cost-effectiveness was questionable for low-income settings and Asia. Mammography screening was more cost-effective with biennial screening compared to annual screening and single reading using computer-aided detection vs double reading. No information on the cost-effectiveness of ultrasonography was found, and there is much uncertainty on the cost-effectiveness of CBE because of methodological limitations.