Methods for Development of the European Commission Initiative on Breast Cancer Guidelines Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement The Canadian National Breast Screening Study: responses to controversy. The mammographic screening trials: commentary on the recent work by Olsen and Gøtzsche. Screening for Breast Cancer: Recommendations and Rationale Benefits, Harms, and Cost-Effectiveness of Supplemental Ultrasonography Screening for Women With Dense Breasts Women's perception of the benefits of mammography screening: population-based survey in four countries. Cost-Effectiveness of Extending Screening Mammography Guidelines To Include Women 40 to 49 Years of Age Evidence on screening for breast cancer from a randomized trial More Informative Abstracts of Articles Describing Clinical Practice Guidelines The effect of information about overdetection of breast cancer on women's decision-making about mammography screening: study protocol for a randomised controlled trial The Canadian National Breast Screening Study-1: Breast Cancer Mortality after 11 to 16 Years of Follow-up: A Randomized Screening Trial of Mammography in Women Age 40 to 49 Years Use of a decision aid including information on overdetection to support informed choice about breast cancer screening: a randomised controlled trial Experience with breast cancer, pre-screening perceived susceptibility and the psychological impact of screening. The effect of a couples intervention to increase breast cancer screening among korean americans. The Canadian National Breast Screening Study: A Perspective on Criticisms Quality of life valuations of mammography screening Factors influencing elderly women's mammography screening decisions: implications for counseling Breast Cancer Risk Perception, Benefits of and Barriers to Mammography Adherence Among a Group of Iranian Women Community organization to promote breast cancer screening among women ages 50-75. Cumulative Probability of False-Positive Recall or Biopsy Recommendation After 10 Years of Screening Mammography Prognosis, treatment, and recurrence of breast cancer for women attending or not attending the Screening Mammography Program of British Columbia
In December 2003 , the European Council identified best practice as key for ensuring development of high- quality cancer-screening programs . To support national policies on cancer control , the European Union institutions progressed several initiatives on cancer . The European Commission ( EC ) Initiative on Breast Cancer ( ECIBC ) is the most recent of these projects and the most implementation driven . Within this initiative , the European Guidelines for Breast Cancer Screening and Diagnosis ( in short , European Breast Guidelines ) are being developed ( http://ecibc.jrc.ec.europa.eu/ ) . Guidelines are approaches to generally improve prevention , diagnosis , treatment , and follow-up of diseases , overcoming inappropriate variations by providing recommendations for best care . The new era of guidelines promises recommendations that are based on the best available evidence summarized in systematic review s while providing the necessary flexibility needed to individualize decisions . The best methods for development of practice guidelines have experienced intense elaboration and attention during the past decades ( 17 ) . The impetus for this attention has been the change from expert- or consensus-based to evidence -based health care recommendations . Although this change in terminology should express the shift from un systematic development of guidelines to systematic and trustworthy recommendations , it is often misunderstood and misconstrued as meaning that experts are now meaningless in the process or as if consensus through discussion is a matter of the past . Neither is correct . Experts from various disciplines and consensus as a result of deliberation remain a mainstay of health care guideline development ( 810 ) . These experts are responsible for prioritization of questions that should be addressed in guidelines ; judgments that result from interpretation of evidence , including the rating of the certainty of the available evidence ; and decisions about how the judgments on the different criteria bear on recommendations . What has changed over time in guideline development are the rules , the structure and explicitness of the process , and the guideline product . Indeed , review s of guideline development methodology and how guidelines can be improved have led to more structured and documented processes that allow a reduction of bias and provide balanced views of appropriately composed guideline panels ( 2 , 5 , 6 ) . Core components for trustworthy guideline development ( 13 , 5 , 7 , 11 ) include that guidelines be developed by a knowledgeable , multidisciplinary panel of experts and representatives from key affected groups ; be based on a systematic review of the existing evidence ; consider important patient subgroups and patient preferences as appropriate ; be based on an explicit and transparent process that minimizes distortions , biases , and conflicts of interest ( 12 ) ; provide a clear explanation of the logical relationships between alternative care options and health outcomes and provide ratings of both the quality of evidence and the strength of the recommendations ( 1316 ) ; and be reconsidered and revised as appropriate when important new evidence warrants modifications . In addition , greater transparency in linking the considered research evidence and the recommendations , as well as the requirement of making structured expert judgments , represents a shift in the guideline development paradigm ( 5 , 11 , 1719 ) . At the same time , developing guidelines for a large number of member states and those that aim to adapt the guidelines poses challenges , such as the feasibility of implementing strategies that may exist in some member countries but not others ( for example , organized population -based screening in Italy but not Greece ) . Addressing these challenges requires considerations that extend beyond strictly clinical efforts in guideline development and mastering the many factors that influence recommendations and their implementation . This article describes the rationale , methods , and processes the ECIBC has adopted to develop the European Breast Guidelines in the context of evolving international st and ards . It also describes an innovative approach to presenting , disseminating , and accelerating implementation of recommendations . Guideline Methodology and Development To adhere to the core requirements for guideline development , the EC has taken several steps . First , it selected , via an open call ( https://ecibc.jrc.ec.europa.eu/ guidelines -team ) , a panel with broad representation of expertise , knowledge , and background , which includes patients , health care professionals , epidemiologists , guideline method ologists , and others ( Appendix ) . These individuals voluntarily participate in the ECIBC and compose the guidelines development group ( GDG ) . Second , it ensured that all recommendations were supported by systematic review s of the evidence conducted by independent scientists from Cochrane Iberoamricathe systematic review team (SRT)following st and ard Cochrane Collaboration methods ( 20 , 21 ) . Third , because this is a women-centered initiative , we included women advocates in the GDG as full voting guideline group members . We separately considered important subgroups of women during recommendation development ( for example , different age groups ) , and we specifically focused on evidence that supports best ways of communicating this information to women to inform their decisions . Fourth , we applied EC conflict of interest rules ( http://ecibc.jrc.ec.europa.eu/rules ) , which are consistent with international recommendations , and used GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) Evidence to Decision ( EtD ) frameworks to minimize the influence of competing interests on the recommendations ( 12 , 17 , 18 ) . These EtD frameworks help guideline panels use evidence in a structured , transparent way to inform decisions with a series of criteria , such as anticipated harms and benefits of the options considered , the certainty of the evidence for those effects , and the costs and feasibility of the options , to help them reach their decision . Fifth , using the GRADE approach to guideline development and its EtD frameworks , we focused our questions and recommendations on outcomes that matter to women and provided a rating of the certainty or quality of evidence and the strength of recommendations that is widely accepted as the reference st and ard ( Figures 1 and 2 ) . Sixth , our evidence review s are up to date when the recommendations are formulated , and we engage in international stakeholder feedback to ensure that recommendations remain timely and relevant to public health and clinical practice . The ECIBC is committed to review ing and updating the recommendations as required when new evidence becomes available . The general process is explained in Figure 3 and is based on the Guidelines International NetworkMcMaster Guideline Development Checklist ( https://hei grade .mcmaster.ca/ guideline -development/using-checklist ) ( 5 ) . Figure 1 . According to GRADE , certainty , quality , strength of evidence , or confidence in the estimate of effect is determined on the basis of a systematic review of the evidence for each outcome ( based on the domains risk of bias , indirectness , imprecision , inconsistency , and publication bias that lower certainty and , usually only for nonr and omized studies , large effects , doseresponse relations and opposing plausible residual confounding that may increase the certainty ) . For recommendations , the overall certainty is determined across outcomes based on the lowest certainty outcome among those critical for decision making for the specific context . The guidelines development group applies the GRADE Evidence -to-Decision frameworks to make recommendations that are made available on the European Commission Web site . ( Reproduced from reference 15 , with permission from Schnemann HJ . ) . GRADE = Grading of Recommendations Assessment , Development and Evaluation . Figure 2 . GRADE EtD frameworks . The GRADE EtD frameworks as available in the GRADE pro software ( www . grade pro.org ) . They help with structuring the entire guideline process into 4 sections and support the conduct of guideline group meetings , presentation , and implementation . They clarify the perspective that is taken by the guideline panel or decision maker and the type of question that is asked in the question section . The section on assessment includes the criteria if the problem is a priority , the balance of health benefits and harms , values and preferences related to the outcomes , cost , re sources and cost-effectiveness , equity , acceptability , and feasibility . Conclusions provide the decision or recommendation with a justification and implementation , as well as research considerations . The presentation function supports the conduct of guideline group meetings and facilitates the output of EtD frameworks to other implementation tools , such as Web sites , h and -held apps , and interactive decision aids . EtD = Evidence to Decision ; GRADE = Grading of Recommendations Assessment , Development and Evaluation ; HTA = health technology assessment ; PICO = population , intervention , comparators , and outcomes . Figure 3 . Approach to guideline development used by the European Commission Initiative on Breast Cancer . The European Commission JRC has oversight of the organization , budgeting , planning , and training . The JRC also manages conflicts of interest , documents all aspects of the work , and manages the membership and group processes . The guideline development group and JRC formulate the questions and work with the systematic review team on identifying and assessing the evidence . The guidelines development group is responsible for developing the recommendations . The JRC is responsible for most other aspects as described in the figure under dissemination , implementation , and updating . JRC = Joint Research Centre ; PICO = population , intervention , comparator , and outcomes . ( Reproduced with adaptation to the JRC process from Breast cancer is the most common cancer type in women and the fourth leading cause of cancer death in the United States ( 1 ) . The goal of screening is to reduce morbidity and mortality , both specific to breast cancer and overall , with acceptable tradeoffs ( 2 , 3 ) . The most commonly used screening test is mammography . Recommended strategies vary for breast cancer screening in average-risk women . Ages to start and discontinue mammography , screening intervals , the role of imaging methods other than mammography , and the role of clinical breast examination ( CBE ) have been points of disagreement among guideline developers . Purpose and Target Population The goal of this American College of Physicians ( ACP ) guidance statement is to critically review selected guidelines from around the world and their included evidence to assist clinicians in making decisions about breast cancer screening in asymptomatic women with average risk for breast cancer . Included screening methods are CBE and breast imaging ( that is , mammography , ultrasonography , magnetic resonance imaging [ MRI ] , and digital breast tomo synthesis [ DBT ] ) . This guidance statement does not address breast self-examination because no evaluated guideline recommends it for screening . The target population for this guidance statement is women with average risk for breast cancer . The target audience is all clinicians . Age is the single most important risk factor for breast cancer . Included guidelines generally define average-risk women as those who do not have a personal history of breast cancer or a previous diagnosis of a high-risk breast lesion , are not at high risk for breast cancer due to genetic mutations known to increase that risk ( such as BRCA1/2 gene mutation or another familial breast cancer syndrome ) , and were not exposed to radiation therapy to the chest in childhood ( 4 , 5 ) . However , definitions of average risk vary among guidelines . In addition , although risk factors ( including early menarche , late menopausal onset , oral contraceptive or menopausal hormone therapy , increased breast density on mammography , and a family member with a history of postmenopausal breast cancer ) may put a woman at greater risk for breast cancer than women without these factors , the evaluated guidelines generally include women with these factors under the umbrella of average risk . Therefore , our guidance statement applies to these women . Guidelines vary somewhat in target population s and screening methods addressed ( Table [ 411 ] and Appendix ) . Both the U.S. Preventive Services Task Force ( USPSTF ) and the World Health Organization ( WHO ) include women with dense breasts and those with a single family member with breast cancer in their guideline 's target population ( 5 , 6 ) . The Canadian Task Force on Preventive Health Care ( CTFPHC ) guideline also includes women with dense breasts ; however , it explicitly mentions that women with a first-degree relative with breast cancer are considered to be at increased risk and are thus excluded from the guideline ( 7 ) . Table . Summary of Included Recommendations in Assessed Guidelines for Breast Cancer Screening of Average-Risk Women Methods The ACP Clinical Guidelines Committee develops guidance statements on topics where several conflicting guidelines are available . Guidance statements rely on evidence presented or referenced in selected guidelines and accompanying evidence reports ; they do not include de novo review s or search es of the literature outside the body of evidence referenced by the guidelines . The goal of ACP guidance statements is to provide clinicians with a rigorous review of the available guidelines and their included evidence and to develop subsequent guidance based on an assessment of the benefits and harms reported by each guideline and its evidence . Unlike ACP guidelines , guidance statements are not derived from a systematic evidence review and hence do not use GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) ( 12 ) to assess the quality of evidence or strength of recommendations . Data Sources and Guideline Selection We search ed the National Guideline Clearinghouse and the Guidelines International Network library for breast cancer screening guidelines from national organizations that addressed breast imaging ( that is , mammography , ultrasonography , MRI , or DBT ) and CBE in women and were published in English between 1 January 2013 and 15 November 2017 . We search ed Web sites housing the selected guidelines for up date s on 10 December 2018 . We excluded guidelines that addressed specific population s ( such as pregnant women and women at increased risk for breast cancer ) or were more than 5 years old ( thus considered inactive ) . We also excluded guidelines that directly endorsed another guideline , such as that of the American Academy of Family Physicians , which endorsed the USPSTF guideline . Our search yielded 3 guidelines , from the American College of Radiology ( published in 2017 ; literature search end date , February 2016 ) ( 9 ) , American Cancer Society ( ACS ) ( published in 2015 ; literature search end date , March 2014 ) ( 4 ) , and USPSTF ( published in 2016 ; literature search end date , June 2015 ) ( 5 ) . We also selected 3 guidelines not identified in either data base but commonly used in clinical practice , from the National Comprehensive Cancer Network ( NCCN ) ( published in 2018 ; literature search end date not reported ) ( 10 ) , WHO ( published in 2014 ; literature search end date , December 2012 ) ( 6 ) , and American College of Obstetricians and Gynecologists ( published in 2017 ; literature search end date not applicable ) ( 8) . In addition , we selected the CTFPHC guideline , which was up date d after our initial search ( published in 2018 ; literature search end date , January 2017 ) ( 7 ) . The American College of Obstetricians and Gynecologists guideline was based on guidelines from the ACS , NCCN , and USPSTF and supporting evidence review s. Critical Appraisal Five co authors independently review ed , assessed , and scored each guideline using the AGREE II ( Appraisal of Guidelines for Research and Evaluation II ) instrument ( 13 , 14 ) ( Appendix Table 1 ) . Appendix Table 1 . Scaled AGREE II Domain Scores for Each Guideline and Overall Assessment Clinician Peer Review The guidance statement was peer- review ed through Annals of Internal Medicine and by ACP Regents and Governors , who represent ACP members at the regional and international level . Public Member Review The development process for the guidance statement included participation by public members ( 2 of the Clinical Guidelines Committee and 7 of ACP 's Public Panel ) to share their perspectives , values , and preferences . Critical Appraisal of Evaluated Guidelines The major difference between high- and low-scoring guidelines ( Appendix Table 1 ) was methodology . Guidelines from ACS ( 4 ) , CTFPHC ( 7 ) , USPSTF ( 5 ) , and WHO ( 6 ) scored highest on the AGREE II instrument , whereas those from the American College of Obstetricians and Gynecologists ( 8) , American College of Radiology ( 9 ) , and NCCN ( 10 ) scored lowest . In addition to our review of each guideline , we examined the evidence supporting the 4 that scored highest ( ACS , CTFPHC , USPSTF , and WHO ) . We also considered recommendations for adoption or adaptation from these 4 guidelines when developing our own guidance . Several factors were important in considering guideline quality . The ACS , CTFPHC , USPSTF , and WHO guidelines best articulated benefits , harms , and strength of the evidence and how these link to recommendations . The lower-scoring guidelines often inadequately described how they considered these factors in developing the recommendations , or they relied on lower- quality evidence . The guidelines varied in the studies they reported , weighting of observational or modeling studies relative to r and omized controlled trials ( RCTs ) , and emphasis on relative versus absolute effects . The guidelines rarely addressed the small absolute effect on breast cancer mortality ; the long lead time to any reduction in this mortality , especially in women with estimated life expectancy less than 15 to 20 years ; and the low incidence of breast cancer for women younger than 60 years . Mammography Depending on the guideline , the recommended age to discuss initiating screening is 40 years ( 4 , 5 , 8) and the recommended age to start screening ranges from 40 ( 9 , 10 ) to 45 ( 4 ) to 50 ( 58 ) years . Most guidelines agree to screen average-risk women with  mammography  between ages 50 and 74 years . However , WHO and CTFPHC recommend that screening in women aged 50 to 69 years should include shared decision making because screening is conditional on a woman 's values and preferences . For women aged 70 to 75 years , WHO recommends screening only in the context of both rigorous research and shared decision making . Other areas of disagreement include screening in women aged 40 to 49 years , screening in women aged 75 years or older , and recommended screening intervals ( Table ) . Intervals range from annual ( particularly in women aged 40 to 49 years ) to biennial or triennial . Guidelines from ACS , USPSTF , and WHO conclude that a close balance exists between screening benefits and harms for women in their 40s ( for ACS , 40 to 44 years ) and that decisions are influenced by patient preferences . The WHO guideline suggests population -based screening programs in women aged 40 to 49 years only in the context of rigorous research , monitoring , and evaluation and if shared decision-making strategies are implemented . The CTFPHC conditionally recommends against screening in women aged 40 to 49 years ( without a first-degree family history of breast cancer ) ; however , it states that some women in this age group may wish to be screened and that clinicians should engage in shared decision making with women who express interest ( Appendix ) . Appendix Table 2 summarizes the available data from the 4 guidelines with the highest AGREE II scores ( ACS , CTFPHC , USPSTF , and WHO ) . Appendix Table 2 . Summary of Evidence on Screening The U.S. Preventive Services Task Force ( USPSTF ) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms . It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance . The USPSTF does not consider the costs of providing a service in this assessment . The USPSTF recognizes that clinical decisions involve more considerations than evidence alone . Clinicians should underst and the evidence but individualize decision making to the specific patient or situation . Similarly , the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms . Summary of Recommendations and Evidence The USPSTF recommends biennial screening mammography for women aged 50 to 74 years . ( B recommendation ) The decision to start screening  mammography  in women prior to age 50 years should be an individual one . Women who place a higher value on the potential benefit than the potential harms may choose to begin biennial screening between the ages of 40 and 49 years . ( C recommendation ) For women who are at average risk for breast cancer , most of the benefit of mammography results from biennial screening during ages 50 to 74 years . Of all of the age groups , women aged 60 to 69 years are most likely to avoid breast cancer death through mammography screening . While screening mammography in women aged 40 to 49 years may reduce the risk for breast cancer death , the number of deaths averted is smaller than that in older women and the number of false-positive results and unnecessary biopsies is larger . The balance of benefits and harms is likely to improve as women move from their early to late 40s . In addition to false-positive results and unnecessary biopsies , all women undergoing regular screening mammography are at risk for the diagnosis and treatment of noninvasive and invasive breast cancer that would otherwise not have become a threat to their health , or even apparent , during their lifetime ( known as overdiagnosis ) . Beginning mammography screening at a younger age and screening more frequently may increase the risk for overdiagnosis and subsequent overtreatment . Women with a parent , sibling , or child with breast cancer are at higher risk for breast cancer and thus may benefit more than average-risk women from beginning screening in their 40s . Go to the Clinical Considerations section for information on implementation of the C recommendation . The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women aged 75 years or older . ( I statement ) The USPSTF concludes that the current evidence is insufficient to assess the benefits and harms of digital breast tomo synthesis ( DBT ) as a primary screening method for breast cancer . ( I statement ) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of adjunctive screening for breast cancer using breast ultrasonography , magnetic resonance imaging ( MRI ) , DBT , or other methods in women identified to have dense breasts on an otherwise negative screening mammogram . ( I statement ) These recommendations apply to asymptomatic women aged 40 years or older who do not have preexisting breast cancer or a previously diagnosed high-risk breast lesion and who are not at high risk for breast cancer because of a known underlying genetic mutation ( such as a BRCA1 or BRCA2 gene mutation or other familial breast cancer syndrome ) or a history of chest radiation at a young age . See Figure 1 for a summary of the recommendation and suggestions for clinical practice . Figure 1 . Screening for breast cancer : clinical summary . Appendix Table 1 describes the USPSTF grade s , and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit . Appendix Table 1 . What the USPSTF Grade s Mean and Suggestions for Practice Appendix Table 2 . USPSTF Levels of Certainty Regarding Net Benefit Supplement . Consumer Fact Sheet Rationale Importance Breast cancer is the second-leading cause of cancer death among women in the United States . In 2015 , an estimated 232000 women were diagnosed with the disease and 40000 women died of it . It is most frequently diagnosed among women aged 55 to 64 years , and the median age of death from breast cancer is 68 years ( 1 ) . Benefit and Harms of Screening and Early Treatment The USPSTF found adequate evidence that mammography screening reduces breast cancer mortality in women aged 40 to 74 years . The number of breast cancer deaths averted increases with age ; women aged 40 to 49 years benefit the least and women aged 60 to 69 years benefit the most . Age is the most important risk factor for breast cancer , and the increased benefit observed with age is at least partly due to the increase in risk . Women aged 40 to 49 years who have a first-degree relative with breast cancer have a risk for breast cancer similar to that of women aged 50 to 59 years without a family history . Direct evidence about the benefits of screening mammography in women aged 75 years or older is lacking . The USPSTF found adequate evidence that screening for breast cancer with mammography results in harms for women aged 40 to 74 years . The most important harm is the diagnosis and treatment of noninvasive and invasive breast cancer that would otherwise not have become a threat to a woman 's health , or even apparent , during her lifetime ( that is , overdiagnosis and overtreatment ) . False-positive results are common and lead to unnecessary and sometimes invasive follow-up testing , with the potential for psychological harms ( such as anxiety ) . False-negative results ( that is , missed cancer ) also occur and may provide false reassurance . Radiation-induced breast cancer and result ing death can also occur , although the number of both of these events is predicted to be low . The USPSTF found inadequate evidence on the benefits and harms of DBT as a primary screening method for breast cancer . Similarly , the USPSTF found inadequate evidence on the benefits and harms of adjunctive screening for breast cancer using breast ultrasonography , MRI , DBT , or other methods in women identified to have dense breasts on an otherwise negative screening mammogram . In both cases , while there is some information about the accuracy of these methods , there is no information on the effects of their use on health outcomes , such as breast cancer incidence , mortality , or overdiagnosis rates . USPSTF Assessment The USPSTF concludes with moderate certainty that the net benefit of screening  mammography  in women aged 50 to 74 years is moderate . The USPSTF concludes with moderate certainty that the net benefit of  screening mammography  in the general population of women aged 40 to 49 years , while positive , is small . The USPSTF concludes that the evidence on  mammography screening  in women age 75 years and older is insufficient , and the balance of benefits and harms can not be determined . The USPSTF concludes that the evidence on DBT as a primary screening method for breast cancer is insufficient , and the balance of benefits and harms can not be determined . The USPSTF concludes that the evidence on adjunctive screening for breast cancer using breast ultrasound , MRI , DBT , or other methods in women identified to have dense breasts on an otherwise negative screening mammogram is insufficient , and the balance of benefits and harms can not be determined . Clinical Considerations Benefit of Screening The results of the meta- analysis of clinical trials from the systematic evidence review commissioned by the USPSTF are summarized in Table 1 . Over a 10-year period , screening 10000 women aged 60 to 69 years will result in 21 ( 95 % CI , 11 to 32 ) fewer breast cancer deaths . The benefit is smaller in younger women : Screening 10000 women aged 50 to 59 years will result in 8 ( CI , 2 to 17 ) fewer breast cancer deaths , and screening 10000 women aged 40 to 49 years will result in 3 ( CI , 0 to 9 ) fewer breast cancer deaths ( 2 , 3 ) . Most of these trials began enrollment more than 30 years ago , and these estimates may not reflect the current likelihood of avoiding a breast cancer death with contemporary screening mammography technology . Mammography imaging has since improved , which may result in more tumors being detected at a curable stage today than at the time of these trials . However , breast cancer treatments have also improved , and as treatment improves , the advantage of earlier detection decreases , so that some of the women who died of breast cancer in the nonscreened groups in these trials would survive today . Table 1 . Breast Cancer Deaths Avoided ( 95 % CI ) per 10 000 Women Screened by Repeat Screening Mammography Over 10 Years : Data From R and omized , Controlled Trials * Harms of Screening The most important harm of screening is the detection and treatment of invasive and noninvasive cancer that would never have been detected , or threaten health , in the absence of screening ( overdiagnosis and overtreatment ) . Existing science does not allow for the ability to determine precisely what proportion of cancer diagnosed by mammography today reflects overdiagnosis , and estimates vary widely depending on the data source and method of calculation used ( 2 , 4 ) . In the United States , the rate of diagnosis of invasive plus noninvasive breast cancer increased by 50 % during the era of mammography screening ( Figure 2 ) ( 5 ) . It is not possible to know with certainty what proportion of that increase is due to overdiagnosis and what proportion reflects other reasons for a rising incidence . If overdiagnosis is the only explanation for the increase , 1 in 3 women diagnosed with breast cancer today is being treated for cancer that would never have been discovered or caused her health problems in the absence of screening . The best estimates from r and omized , controlled trials ( RCTs ) evaluating A t least since 1985 , there has been concern in some quarters that the Canadian National Breast Screening Study ( NBSS ) results 1'2 would fail to show a benefit from combined mammographic and clinical screening for breast cancer in women age 40 - 49 years . In the United States , in the spring of 1992 , the controversy about the benefits of screening women age 40 - 49 for the early detection of breast cancer erupted in the media . 3 - 7 The center of attention was the unpublished results of the NBSS . However , the center of controversy is the conflicting guidelines on breast screening for women age 40 - 49 . The very familiar guidelines of the American Cancer Society and the American College of Radiology ( ACR ) exhort women in this age group to " do themselves a favor " and get a mammogram . Although a number of prestigious professional associations have chosen to endorse these guidelines , others have not , including the US Preventive Services Task Force , the American College of Physicians , the Canadian Workshop Group , 8 the National Cancer Institute of Canada , an expert panel in the United Kingdom , 9 and the European Group for Breast Screening . 1 ° To underst and the nature of the controversy , it is helpful to review both the NBSS and published evidence from other screening studies . The Canadian NBSS was design ed to answer two major questions J , 2 First , in women age 40 - 49 , does annual mammography combined with annual physical examination of the breast for 3 or 4 years reduce the mortality rate from breast cancer as compared with a single physical examination alone ? Second , in women age 50 - 59 , how much does mammography contribute to mortality reduction over and above that achieved by physical examination alone when the comparison is annual mammography combined with physical examination versus annual physical examination alone ? The NBSS screened 89,835 women at 15 centers across Canada from 1980 - 1988 , with each woman individually r and omized to the mammography arm or the nonmammography arm of the study . Approximately 50,000 participants were 40 - 49 on entry and the remainder were 50 - 59 years of age . To be eligible , women were required to sign informed consent forms , to never have had a diagnosis of breast cancer , © 1992 by The Jacobs Institute of Women ' s Health 1049 - 68 CA A Cancer Journal for Clinicians Since the publication of the results of the Greater New York Trial and the Swedish Two-County Trial in the 1970s and 1980s , there has been a general consensus that screening for breast cancer with mammography reduces mortality from the disease . The results of these pioneering trials for the most part have been subsequently confirmed by later trials in Sweden , Canada , and the United Kingdom . Although some issues endure , most notably those regarding cost-effectiveness of screening in particular age groups , as well as concerns about harms associated with false positive results , the evidence that screening reduces deaths from breast cancer has steadily increased , and the consensus regarding the benefit of screening has grown stronger . The evidence that screening with mammography is associated with a lower breast cancer death rate recently was challenged when The Lancet published a research letter by Olsen and Gotzsche ( OG ) describing their overview of the mammographic screening trials . OG asserted that “ ... the reliable evidence does not indicate any survival benefit of mass screening for breast cancer , ” and they maintained that screening leads to more aggressive treatment ; thus , screening is not only without benefit , but in addition to representing a waste of health re sources , it actually results in net harms . This article has generated considerable print and electronic media attention , with a spectrum of opinions ranging from complete support for the conclusions of OG to complete dissent . Yet , despite the public exchange , the OG report has failed to convince institutional leaders in the United Kingdom , Sweden , the Netherl and s , or the United States to change screening policy . Most have publicly reaffirmed the current recommendations supporting regular mammography . Having thoroughly considered all available information , including the OG report , the US Preventive Services Task Force retained its current recommendation that women have regular mammograms every one to two years , and in fact , exp and ed the recommendation to include women in their forties . In addition , 10 leading medical organizations published a full-page open letter in the New York Times on January 31 , 2002 , supporting the value of early breast cancer detection . In our opinion , which is based on evidence accrued over decades of scientific research on breast cancer screening , and countless , independent expert peer review s of the study design s , data , and conclusions of the trials , the scientific foundation for the value of early breast cancer detection with mammography is sound . To see why , consider Figure 1 , which summarizes the most recently published results of the mammographic screening trials . The results indicate that there is a statistically significant 24 % reduction in  breast cancer mortality associated with an invitation to screening .  The distinction between “ invited to screening ” versus “ screened ” becomes clear when you consider that a r and omized trial of screening examines mortality rates in the study arm offered screening versus the study arm offered usual care . Mr. Duffy is Principal Scientist , Cancer Research UK , London , Engl and Summary of the Recommendations The U.S. Preventive Services Task Force ( USPSTF ) recommends screening mammography , with or without clinical breast examination ( CBE ) , every 1 to 2 years for women aged 40 and older . This is a grade B recommendation . ( See Appendix Table 1 for a description of the USPSTF classification of recommendations . ) The USPSTF found fair evidence that mammography screening every 12 to 33 months significantly reduces mortality from breast cancer . ( See Appendix Table 2 for a description of the USPSTF classification of levels of evidence . ) Evidence is strongest for women aged 50 to 69 , the age group generally included in screening trials . For women aged 40 to 49 , the evidence that screening mammography reduces mortality from breast cancer is weaker , and the absolute benefit of mammography is smaller , than it is for older women . Most , but not all , studies indicate a mortality benefit for women undergoing mammography at ages 40 to 49 , but the delay in observed benefit in women younger than 50 makes it difficult to determine the incremental benefit of beginning screening at age 40 rather than at age 50 . The absolute benefit is smaller because the incidence of breast cancer is lower among women in their 40s than it is among older women . The USPSTF concluded that the evidence is also generalizable to women aged 70 and older ( who face a higher absolute risk of breast cancer ) if their life expectancy is not compromised by comorbid disease . The absolute probability of benefits of regular mammography  increases along a continuum with age , whereas the likelihood of harms from screening ( false-positive results and unnecessary anxiety , biopsies , and cost ) diminishes from ages 40 to 70 . The balance of benefits and potential harms , therefore , grows more favorable as women age . The precise age at which the potential benefits of mammography justify the possible harms is a subjective choice . The USPSTF did not find sufficient evidence to specify the optimal screening interval for women aged 40 to 49 ( see Clinical Considerations ) . The USPSTF concludes that the evidence is insufficient to recommend for or against routine CBE alone to screen for breast cancer . This is a grade I recommendation . No screening trial has examined the benefits of CBE alone ( without accompanying mammography ) compared to no screening , and design characteristics limit the generalizability of studies that have examined CBE . The USPSTF could not determine the benefits of CBE alone or the incremental benefit of adding CBE to mammography . The USPSTF therefore could not determine whether potential benefits of routine CBE outweigh the potential harms . The USPSTF concludes that the evidence is insufficient to recommend for or against teaching or performing routine breast self-examination ( BSE ) . This is a grade I recommendation . The USPSTF found poor evidence to determine whether BSE reduces breast cancer mortality . The USPSTF found fair evidence that BSE is associated with an increased risk of false-positive results and biopsies . Because of design limitations of published and ongoing studies of BSE , the USPSTF could not determine the balance of benefits and potential harms of BSE . Clinical Considerations The precise age at which the benefits from screening mammography justify the potential harms is a subjective judgment and should take into account patient preferences . Clinicians should inform women about the potential benefits ( reduced chance of dying from breast cancer ) , potential harms ( for example , false-positive results , unnecessary biopsies ) , and limitations of the test that apply to women their age . Clinicians should tell women that the balance of benefits and potential harms of mammography improves with increasing age for women between the ages of 40 and 70 . Women who are at increased risk for breast cancer ( for example , those with a family history of breast cancer in a mother or sister , a previous breast biopsy revealing atypical hyperplasia , or first childbirth after age 30 ) are more likely to benefit from regular mammography than women at lower risk . The recommendation for women to begin routine screening in their 40s is strengthened by a family history of breast cancer having been diagnosed before menopause . The USPSTF did not examine whether women should be screened for genetic mutations ( BRCA1 and BRCA2 ) that increase the risk of developing breast cancer , or whether women with genetic mutations might benefit from earlier or more frequent screening for breast cancer . In the trials that demonstrated the effectiveness of mammography in lowering breast cancer mortality , screening was performed every 12 to 33 months . For women aged 50 and older , there is little evidence to suggest that annual mammography is more effective than mammography done every other year . For women aged 40 to 49 , available trials also have not reported a clear advantage of annual mammography over biennial mammography . Nevertheless , some experts recommend annual mammography based on the lower sensitivity of the test and on evidence that tumors grow more rapidly in this age group . The precise age at which to discontinue screening mammography is uncertain . Only two r and omized , controlled trials enrolled women older than 69 , and no trials enrolled women older than 74 . Older women face a higher probability of developing and dying of breast cancer but also have a greater chance of dying of other causes . Women with comorbid conditions that limit their life expectancy are unlikely to benefit from screening . Clinicians should refer patients to  mammography screening centers with proper accreditation and quality assurance st and ards to ensure accurate imaging and radiographic interpretation . Clinicians should adopt office systems to ensure timely and adequate follow-up of abnormal results . A listing of accredited facilities is available at www . fda .gov/cdrh/mammography/certified.html . Clinicians who advise women to perform BSE or who perform routine CBE to screen for breast cancer should underst and that there is currently insufficient evidence to determine whether these practice s affect breast cancer mortality and that they are likely to increase the incidence of clinical assessment s and biopsies . The brief review of the evidence that is normally included in USPSTF recommendations is available in the complete recommendation and rationale statement on the USPSTF Web site ( www.preventiveservices.ahrq.gov ) . Recommendations of Others Nearly all North American organizations support mammography screening , although groups vary in the recommended age to begin screening , the interval for screening , and the role of CBE . The American Medical Association ( AMA ) ( 1 ) , the American College of Radiology ( ACR ) ( 2 ) , and the American Cancer Society ( ACS ) ( 3 ) all support screening with mammography and CBE beginning at age 40 . The American College of Obstetricians and Gynecologists ( ACOG ) ( 4 ) supports screening with mammography beginning at age 40 and CBE beginning at age 19 . The Canadian Task Force on Preventive Health Care ( CTFPHC ) ( 5 ) , the American Academy of Family Physicians ( AAFP ) ( 6 ) , and the American College of Preventive Medicine ( ACPM ) ( 7 ) recommend beginning mammography for average-risk women at age 50 . The AAFP and ACPM recommend that mammography in high-risk women begin at age 40 , and the AAFP recommends that all women aged 40 to 49 be counseled about the risks and benefits of mammography before making decisions about screening ( 6 , 7 ) . A 1997 Consensus Development Panel convened by the U.S. National Institutes of Health concluded that the evidence was insufficient to determine the benefits of mammography among women aged 40 to 49 . This panel recommended that women aged 40 to 49 should be counseled about potential benefits and harms before making decisions about mammography ( 8) . In 2001 , the CTFPHC concluded there was insufficient evidence to recommend for or against mammography in women 40 to 49 ( 9 ) . Organizations differ on their recommendations for the appropriate interval for mammography .  Annual mammography is recommended by the AMA , ACR , and ACS ( 1 - 3 ) . Mammography every 1 to 2 years is recommended by the CTFPHC , AAFP , and ACPM ( 5 - 7 ) . The ACOG recommends mammography every 1 to 2 years for women aged 40 to 49 and annually for women aged 50 and older ( 4 ) . In its 2001 report , the CTFPHC recommends against teaching  BSE  to women aged 40 to 69 ( 10 ) . The AMA , ACS , ACOG , and AAFP support teaching BSE ( 1 , 3 , 4 , 6 ) Editors ' Notes Context Many states have enacted laws that require mammography facilities to advise women with dense breasts and a negative mammography to consider supplemental testing with their providers . Contribution Three vali date d microsimulation models compared breast cancer outcomes , quality -adjusted life-years gained , and costs for mammography alone versus supplemental ultrasonography after a negative mammography result for women with dense breasts aged 50 to 74 years . Caution Other imaging methods , such as digital breast tomo synthesis , were not assessed . Implication Supplemental ultrasonography screening for women with dense breasts would result in limited health gains and substantially increase costs . Mammographic breast density is a risk factor for breast cancer ( 1 , 2 ) . It also affects mammography performance ( 36 ) . The false-negative rate of screening mammography varies as much as 10-fold from the lowest to the highest categories of breast density ( 5 ) . Because breast density affects cancer risk and the false-negative rate of screening , at least 19 states have enacted legislation requiring that women with dense breasts be told about their breast density after screening mammography and that they should discuss supplemental screening tests , such as ultrasonography , with their providers ( 7 , 8) . Similar legislation is under consideration at the national level ( 9 ) . Breast density notification laws have an uncertain effect on health but could affect millions of women . More than 40 % of women aged 40 to 74 years have dense breasts ( 10 ) , defined in the laws as heterogeneously or extremely dense breast tissue by the American College of Radiology 's Breast Imaging Reporting and Data System ( BI-RADS ) ( 9 , 11 ) . However , the American College of Radiology and other organizations have caution ed legislators , health policymakers , and health care providers to carefully consider the unintended consequences of legislation about breast density notification , including the uncertain harms and benefits of supplemental screening ( 8 , 1215 ) . These concerns are amplified because of the subjective nature of the BI-RADS breast density assessment and the challenges that providers face in accurately assessing and communicating breast cancer risk to their patients . Ultrasonography is often suggested for supplemental screening of women with dense breasts because it is widely available and has relatively low direct medical costs ( 1618 ) . Shortly after Connecticut became the first state to enact a law about breast density notification , as many as 30 % of women with dense breasts at some practice s within the state were having supplemental ultrasonography screening ( 1921 ) . Limited data from clinical trials and observational studies suggest that the addition of h and held ultrasonography screening to mammography for women with dense breasts increases cancer detection rates at the expense of increased biopsies for women without cancer ( 16 , 1922 ) . Moreover , the effect of supplemental ultrasonography screening on long-term outcomes , such as breast cancer mortality and its cost-effectiveness at a population level , are unknown ( 8) . We assessed the potential benefits , harms , and cost-effectiveness of supplemental screening ultrasonography for women with dense breasts using 3 established Cancer Intervention and Surveillance Modeling Network breast cancer models ( 23 ) . The models incorporate evidence from clinical trials and observational studies to estimate the effect of various screening scenarios on breast cancer outcomes , including breast cancer mortality , quality -adjusted life-years ( QALYs ) , and costs ( 24 , 25 ) . The results provide evidence for policymakers considering legislation about breast density notification and for women and providers evaluating screening options for women with dense breasts . Methods We used 3 microsimulation models  developed independently within the National Cancer Institutefunded Cancer Intervention and Surveillance Modeling Network consortium ( www.cisnet.cancer.gov ) : Model E ( Erasmus University Medical Center , Rotterdam , the Netherl and s ) , model G-E ( Georgetown University Medical Center , Washington , DC , and Albert Einstein College of Medicine , Bronx , New York ) , and model W ( University of Wisconsin , Madison , Wisconsin , and Harvard Medical School , Boston , Massachusetts ) . These modeling groups collaborate in the program project grant that supported this study and are described at http://cisnet.cancer.gov/breast/profiles.html and elsewhere ( 2628 ) . Appendix Table 1 outlines the main model differences and assumptions . Our analyses used a lifetime horizon and federal payer perspective . In brief , the models simulated life histories of women who were at risk for breast cancer , had screening , were treated for breast cancer diagnosed by screening or clinical detection , and were at risk for dying of breast cancer and other causes . The models had independent approaches and modeling structures ( 23 ) but used common inputs , including incidence in the absence of screening , mammography performance , treatment effectiveness , and competing causes of death ( 29 ) . The models approximately replicated U.S. breast cancer incidence and mortality trends ( 2628 , 30 ) ( Appendix Figure ) . For this analysis , we used simulated cohorts of women born in 1960 , as described elsewhere ( 24 , 25 ) . Appendix Table 1 . Key Assumptions and Features in the 3 Simulation Models Appendix Figure . Model replication of U.S. incidence and mortality patterns for women aged 30 to 79 y during 19752000 . Model E = Erasmus University Medical Center , Rotterdam , the Netherl and s ; model G-E = Georgetown University Medical Center , Washington , DC , and Albert Einstein College of Medicine , Bronx , New York ; model W = University of Wisconsin , Madison , Wisconsin , and Harvard Medical School , Boston , Massachusetts ; SEER = Surveillance , Epidemiology , and End Results Program . Model Variables At age 40 years , women in the simulated model cohorts were assigned an initial breast density on the basis of the distribution of BI-RADS density categories for premenopausal women in the Breast Cancer Surveillance Consortium ( BCSC ) ( Table 1 ) ( 31 ) . At age 50 years , women were assigned to the same breast density category or the next lower category so the prevalence of breast density categories matched the BCSC observed prevalence for postmenopausal women ( 31 ) . Sensitivity analyses were conducted with model W to examine the effect of reassigning density at both ages 50 and 65 years , on the basis of the BCSC data on the prevalence of breast density for women aged 50 to 64 years ( 44 % with dense breasts ) and 65 years or older ( 33 % with dense breasts ) . In all scenarios , a woman 's modeled risk for breast cancer depended on her age and breast density , on the basis of BCSC data ( Table 1 ) . Table 1 . Key Common Input Used by the 3 Simulation Models : BI-RADS Breast Density Sensitivity and specificity of digital mammography  were determined as a function of age , breast density , and screening interval using BCSC data ( Appendix Table 2 ) ( 32 ) . To our knowledge , the American College of Radiology Imaging Network Protocol 6666 study , a r and omized trial of using h and held ultrasonography to screen women with at least 1 risk factor for breast cancer , was the only controlled study of ultrasonography test performance ( 33 ) . On the basis of this study , experts estimated  screening ultrasonography performance after a negative mammography result for average-risk women . We used a  screening ultrasonography sensitivity of 55 % for women with dense breasts after a negative mammography result . We used a specificity of 94 % , with positive examination results defined as those recommended for biopsy . Models were calibrated so 94 % of ultrasonography screendetected cancer cases were invasive and 6 % were in situ , as seen in published studies ( 16 , 22 ) . Sensitivity analyses evaluated a range of performance characteristics ( Table 2 ) . Appendix Table 2 .  Digital Mammography Sensitivity and Specificity , by Screening Interval , Age Group , and Breast Density Table 2 . Key Common Input Used by the 3 Simulation Models : Screening Ultrasonography Performance Health-related quality -of-life utilities were a function of age ( 34 ) and decremented for breast cancer diagnosis and stage-specific treatment ( 35 ) . Sensitivity analyses included short-term reductions in quality of life for a screening examination ( 0.6 % for 1 week per screening examination ) or a positive screening result ( 10.5 % for 5 weeks ) ( 36 ) . The cost of a digital mammography screen  was $ 138 based on the 2013 Medicare reimbursement rate . Screening ultrasonography does not currently have a specific reimbursement rate , so we used the reimbursement rate for diagnostic breast ultrasonography , which is $ 100 . Sensitivity analyses were also conducted using higher potential reimbursement rates for screening ultrasonography because of its increased work intensity compared with diagnostic ultrasonography .  Diagnostic costs for additional imaging and biopsy after a positive screening mammography result and costs for cancer treatment were based on Medicare reimbursement rates , utilization patterns seen in the BCSC , and estimates from the literature ( 32 , 37 ) . Diagnostic costs after a positive ultrasonography result were assumed to be equal to the biopsy-related costs of diagnostic work-up after a positive mammography result . All costs were in 2013 U.S. dollars . Screening Strategies Primary analysis compared 3 strategies for women aged 50 to 74 years receiving biennial mammography screening  : mammography alone , mammography plus screening ultrasonography after a negative mammography result for women with extremely dense breasts , and mammography plus h and held screening ultrasonography after a negative mammography result for women with heterogeneously or extremely dense breasts ( base case ) . Secondary analyses evaluated the 3 strategies as an annual screening regimen for women aged 40 to 74 years . All strategies were compared with no BACKGROUND Screening programmes are often actively promoted to achieve high coverage , which may result in unrealistic expectations . We examined women 's underst and ing of the likely benefits of  mammography screening . METHODS  Telephone survey of r and om sample s of the female population aged > or = 15 years in the US , UK , Italy , and Switzerl and using three closed questions on the expected benefits of mammography screening . RESULTS A total of 5964 women were contacted and 4140 women ( 69 % ) participated . Misconceptions were widespread : a majority of women believed that screening prevents or reduces the risk of contracting breast cancer ( 68 % ) , that screening at least halves breast cancer mortality ( 62 % ) , and that 10 years of regular screening will prevent 10 or more breast cancer deaths per 1000 women ( 75 % ) . In multivariate analysis higher number of correct answers was positively associated with higher educational status ( odds ratio [ OR ] = 1.44 , 95 % CI : 1.25 , 1.66 ) and negatively with having had a mammography in the last 2 years ( OR = 0.86 , 95 % CI : 0.73 , 1.01 ) . Compared with US women ( reference group ) and Swiss women ( OR = 0.98 , 95 % CI : 0.82 , 1.18 ) respondents in Italy ( OR = 0.61 , 95 % CI : 0.50 , 0.74 ) and the UK ( OR = 0.73 , 95 % CI : 0.60 , 0.88 ) gave fewer correct answers . CONCLUSION In the US and three European countries a high proportion of women overestimated the benefits that can be expected from screening mammography . This finding raises doubts on informed consent procedures within breast cancer screening programmes There is universal agreement [ 1 - 4 ] that women 50 to 69 years of age should undergo  screening mammography  because r and omized , controlled trials have shown that such screening reduces breast cancer mortality in this age group [ 5 , 6 ] . This consensus is bolstered by the results of cost-effectiveness analyses that consistently show that this benefit can be achieved at a reasonable cost [ 7 - 9 ] . In contrast , whether women 40 to 49 years of age should undergo screening mammography is controversial [ 10 - 15 ] . Pooled results of large r and omized , controlled trials have shown no mortality reduction in 40- to 49-year-old women after 7 to 9 years of screening [ 5 , 16 - 18 ] . However , a statistically significant reduction in breast cancer mortality becomes apparent 10 to 14 years after the initiation of screening [ 19 ] . Some authors have argued that this delayed benefit should not be ignored [ 11 ] . However , the reality of constrained health care re sources requires that any benefit from preventive services be achieved at a reasonable cost . Two recently published analyses [ 20 , 21 ] suggest that mammographic screening in younger women may be as cost-effective as screening in older women . The first analysis [ 20 ] calculated average cost-effectiveness by comparing a strategy of screening  40- to 69-year-old women with no screening . Most of the benefit achieved by using this strategy occurs when women are 50 to 69 years of age . Therefore , this analysis did not address whether it is cost-effective to screen women from 40 to 49 years of age in addition to screening them from 50 to 69 years of age . To determine whether the additional benefit obtained by extending screening mammography to women 40 to 49 years of age comes at a reasonable cost would require an incremental cost-effectiveness analysis [ 22 - 26 ] . The second analysis [ 21 ] used a simplified life-expectancy accounting method , did not discount costs or benefits , and associated screening mammography with unsubstantiated mortality reductions ( 30 % for the base case ) . Neither analysis [ 20 , 21 ] included an important aspect of the results of screening mammography trials in 40- to 49-year-old women : that is , no benefit occurs until 10 years after the initiation of screening . An earlier analysis [ 10 ] found screening mammography to be more expensive in women 40 to 49 years of age than in women 50 years of age and older . This previous analysis calculated incremental cost-effectiveness , discounted costs and benefits , and included an estimated delay between the onset of screening and the onset of a mortality benefit . Our analysis extends this work by including up date d pooled results of the r and omized , controlled trials [ 19 ] ; actual delay times before the onset of benefits ; and up date d costs of mammography and treatment of breast cancer . Methods Model We developed a Markov model [ 27 , 28 ] that compared the life expectancy of women undergoing different breast cancer screening strategies . Except for women in whom breast cancer was diagnosed at the initiation of screening , women were healthy at entry into the model . At the end of each 1-year cycle , women were in one of four health states : They remained healthy , developed breast cancer and remained alive , died of breast cancer , or died of another cause . The transition probabilities [ that is , the probabilities of developing breast cancer , dying of breast cancer , and dying of another cause ] were both age- and strategy -dependent . The base-case analysis compared three strategies : 1 ) no screening ; 2 ) screening biennially from 50 to 69 years of age ; and 3 ) screening every 18 months from 40 to 49 years of age , followed by screening biennially from 50 to 69 years of age . The rationale for these screening intervals is discussed below . We calculated the cost-effectiveness of screening in women 50 years of age and older by comparing the first strategy with the second strategy . To determine the incremental cost-effectiveness of screening in 40- to 49-year-old women , we compared the second and third strategies . Costs and benefits were discounted at a rate of 3 % per year for the base-case analysis [ 23 ] . Benefits Trials of screening mammography have shown no reduction in breast cancer mortality among screened women until several years after the initiation of screening [ 5 , 18 , 29 , 30 ] . Meta-analyses and one pooled analysis have shown that among 40- to 49-year-old women , the summary relative risk reduction in breast cancer mortality 7 to 9 years after the initiation of screening is about 1 , indicating no reduction in mortality [ 5 , 16 - 18 ] . Ten to 12 years after the initiation of screening , a nonsignificant trend toward reduced mortality is evident in the screened group ( Figure 1 , left ) [ 5 , 18 , 29 , 30 ] . Recently up date d results show a statistically significant 16 % reduction that occurs 10 to 14 years after the initiation of screening [ 19 ] . For women 50 to 69 years of age , there is an initial period of about 5 years that shows no benefit from screening ( Figure 1 , right ) [ 18 , 29 , 30 ] . Figure 1 . Cumulative breast cancer mortality in  screened  ( black circles ) compared with  nonscreened ( white circles ) women . Left . Right . In our model , for women who start screening at 50 years of age , a 27 % reduction in breast cancer mortality ( Table 1 ) [ 5 ] begins 5 years after the initiation of screening and continues until age 74 years . Although screening ends at 69 years of age , we assumed that women would continue to benefit for another 5 years because of early detection of breast cancer in the last years of screening . For women who begin screening at 40 years of age , a 16 % reduction in breast cancer mortality starts at age 50 years ; this reduction increases to 27 % at age 55 years . Table 1 . Information Used To Calculate Life Expectancy Screening Interval The screening interval in r and omized , controlled trials of screening mammography has varied from 12 to 33 months for women 50 years of age and older . Pooled results of the efficacy of mammography  stratified by length of screening interval do not differ for women in this age group [ 5 ] . From published results [ 5 ] , we determined a 28 % ( 95 % CI , 15 % to 31 % ) reduction in breast cancer mortality in women 50 years of age and older who were screened every 18 to 33 months and a 25 % ( CI , 1 % to 43 % ) reduction in those screened every 12 months . For the base-case analysis , we therefore chose to perform biennial screening in women 50 years of age and older because screening more often only increases cost without increasing the benefits of screening . For the base-case analysis , we used the pooled reduction in breast cancer mortality ( 27 % ) [ 5 ] from all r and omized , controlled trials to determine the cost-effectiveness of biennial screening in 50- to 69-year-old women ; in a sensitivity analysis , we determined the cost-effectiveness of annual screening . The screening interval in r and omized , controlled trials has varied from 12 to 24 months for women 40 to 49 years of age . Pooled results of the efficacy of screening mammography  stratified by length of screening interval did not show a statistically significant reduction in breast cancer mortality for 12-month or 18- to 24-month screening intervals [ 5 ] . As noted above , recently reported pooled results of all r and omized , controlled trials , which on average used a screening interval of 18 months , showed a statistically significant 16 % reduction in breast cancer mortality 10 to 14 years after the initiation of screening [ 19 ] . We therefore assumed that a 16 % reduction in breast cancer mortality would be achieved with screening done every 18 months . This screening interval is consistent with the guidelines of organizations [ 2 , 3 ] that recommend screening every 1 to 2 years for 40- to 49-year-old women . In sensitivity analyses , we calculated the cost-effectiveness of annual and biennial screening , assuming the same 16 % reduction in breast cancer mortality among screened women . Utilities Because there are few data on the utility that women place on life after treatment of breast cancer or the utility placed on living with metastatic breast cancer , we did not include utilities in the base-case analysis . Data from a small Australian study [ 33 ] ( which observed a utility of about 0.8 for life after treatment of breast cancer and a utility of about 0.3 for life with metastatic cancer ) are included in a sensitivity analysis to determine the extent to which cost per year of life saved might differ from cost per quality -adjusted life-year saved . Costs We included three costs : the cost of screening mammographic examinations , the cost of evaluating abnormal mammograms , and the cost of treating breast cancer ( Table 2 ) . Additional details on derivations of costs are given in the Appendix . The cost of screening mammography  was based on the average cost ( $ 91 ) reported by the National Cancer Institute 's National Survey of Mammography Facilities [ 34 ] . This cost was inflated to 1995 dollars ( $ 106 ) by using the consumer price index for medical services . We assumed that women in whom breast cancer was diagnosed continued to undergo screening mammography of the opposite breast , at the same cost , after the initial diagnosis of breast cancer . Table 2 . Information Used to Calculate Costs The cost of evaluating abnormal mammographic results was calculated as a weighted average of procedures that may follow abnormal mammograms . This cost was also inflated to 1995 dollars . The distribution and types of follow-up procedures were based on those reported by the National Cancer Institute 's National Survey of Mammography Facilities [ 35 ] . A range of costs for each procedure was based on data from Medicare , Pennsylvania Blue Cross , Group Health Cooperative , and Kaiser Permanente ( Brown M. Personal communication ) . The percentage of abnormal mammograms was based on the percentage seen with high- quality modern screening mammography ( Table 2 ) [ 36 ] . Population -based data on the cancer stage at diagnosis in screened compared with nonscreened women are sparse . Results in the breast cancer screening project of the Health Insurance Plan of Greater New York that started the end of 1963 have been up date d through December 31 , 1975 . The HIP study is a r and omized trial design ed to test whether periodic screening with clinical examination and mammography results in reduced  breast cancer mortality among women aged 40–64 years at the start . Study women were offered screening examinations ; 65 % appeared for initial examinations and a large majority of these women had at least one of the three additional screenings at annual intervals . The control group of women continued to receive their usual medical care . New data support earlier reported results on benefits . During the nine years following date of entry there were 128 breast cancer deaths in the control group as compared with 91 in the study group ( screenees plus refusers ) . The impact of the screening program continues to be confined to women 50 years of age and over with no benefit at ages 40–49 years . Seven‐year case fatality rates show similar relationships . Several issues related to screening benefit are considered . Of major importance is the observation of no reduction among women under 50 in breast cancer mortality . The possibility that under different screening conditions ( e.g. , with current mammography equipment ) a benefit would be found needs to be investigated . There is a clear need for rapidly determining whether a new r and omized trial is the only way to answer the question and whether experience in the 27 NCI‐ACS demonstration projects can provide useful data . Another critical issue concerns the incremental value of mammography in a screening program . Over an eight‐year period after diagnosis , breast cancer cases that were positive only on mammography when screened had a case fatality rate of 14 % ; this compares with 32 % for cases positive only in the clinical examination and 41 % for cases positive on both modalities . Excluding mammography would have reduced the benefit of screening by an estimated one‐third . With regard to risk associated with screening , it is concluded that the increment in risk result ing from radiation exposure in mammography does not offset the benefits of screening above 50 years of age . Below that age , although the risk increment is small , the risk‐benefit balance is negative because of the absence of a demonstrated benefit . Another source of risk is related to the possible increase in biopsies . Assessment of the HIP experience suggests that only timing of biopsies was affected , but the potential for considerable variation if screening is adopted widely exists . Based on current findings in the HIP study , there appears to be strong support for periodic screening at ages 50 years and over with clinical examination and mammography ; to justify screening under 50 , new information from other studies is required Patients hope that their doctors will correctly identify health problems , clearly articulate sensible options for managing each problem , wisely interpret the best available evidence about probable outcomes associated with each option , sensitively solicit patient preferences for each outcome , and thereby implement practice s that are likely to achieve the results patients care about . Groups of patients hope that doctors will work to prevent , detect , and treat health problems in a way that maximizes the public good achieved with available health care re sources . To meet these dual expectations , doctors face forbidding tasks of clinical decision making . Improved methods for preparing , appraising , and abstract ing overviews of available evidence about a clinical topic can bring a broader range of high- quality information within the busy practitioner 's grasp [ 1 - 4 ] . However , even well- design ed overviews often do not synthesize information about benefits , harms , and costs of medical practice s in a way that facilitates clinical decision making . Clinical practice guidelines have been defined as systematic ally developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances [ 5 ] . Guidelines that are based on sound scientific evidence , and a trustworthy process for judging the value of alternative practice s , could help physicians deal with the information overload they face . Existing practice guidelines , however , vary widely in their quality , and clinicians should carefully consider the validity and applicability of each guideline they read . We propose a structured format for abstract s of articles describing practice guidelines that is based on emerging principles of guideline development and evaluation [ 6 - 13 ] . The proposal is design ed to help readers obtain the key information needed to assess the applicability , importance , and validity of any guideline . The proposed structure for more informative abstract s of articles describing clinical practice guidelines has been review ed and pilot-tested by guideline developers , evaluators , and implementors and by groups of practicing clinicians . Early versions of the proposal were sent to consultants at the National Library of Medicine , the Institute of Medicine , the American College of Physicians ( ACP ) , and the Agency for Health Care Policy and Research . Subsequent versions of the proposal were pilot tested on various published guidelines and were assessed by selected health care organizations for applicability to guidelines under development . An improved proposal was sent to 82 persons active in guideline development , evaluation , and implementation . The Internal Medicine Center to Advance Research and Education circulated the proposal to volunteer practitioners , and the authors solicited feedback from physician and health administrator participants at three national workshops about practice guidelines . The proposal that follows represents an integration of the collective wisdom of our external review ers . ( A glossary of terms used in articles on clinical practice guidelines is supplied in the Appendix . ) Proposed Structure and Content for Abstract s of Articles Describing Clinical Practice Guidelines The proposed structure for abstract s of papers describing clinical practice guidelines is summarized in Table 1 . Key elements of the guideline development process are captured with statements about the principal objective and target of the guideline , the main practice options and outcomes that were considered , the nature of the evidence and values that were analyzed , the main benefits and harms expected from guideline implementation , the key recommendations , and a statement of whether the recommendations have been tested and by whom they have been endorsed . If details about guideline development methods or supporting evidence are published separately , then the abstract should indicate the existence of supporting documents and the most relevant parts of those should be summarized in the abstract . To be included in their entirety in the online bibliographic data bases of the National Library of Medicine , structured abstract s of clinical practice guidelines should not exceed 4096 characters ( approximately 500 words ) in length . Individual journals may have different requirements . Table 1 . Proposed Format for Structured Abstract s of Clinical Practice Guidelines Objective The abstract should state the objective of the guideline by identifying the targeted health problem , the targeted patients and physicians , and the main reason or reasons for developing new recommendations concerning this problem for this population . For guidelines primarily concerned with the management of health conditions , the stage of illness and intent to prevent , diagnose , treat , or palliate the disorder should be specified . For guidelines primarily concerned with health procedures , an intervention and its role in patient management should be defined . Targeted providers , setting s , and patients should be specified so that readers can tell who should do what , where it should be done , and to whom . A statement of objective also may specify why a new guideline is needed and how it should be used . Practice guidelines may be written to clarify or resolve clinical controversies , to communicate important new findings from clinical studies , or to promote more effective , efficient , or consistent physician practice s at less cost or risk to patients . Guidelines may be used concurrently to help physicians and patients make choices ( for example , clinical algorithms ) , retrospectively to compare physician choices to pre-established criteria ( for example , utilization review ) , or prospect ively to set limits on physician choices ( for example , preprocedure approval ) . Options Clinical practice guidelines pertain to clinical decisions . The nature of those decisions should be made explicit by disclosing the main management options considered . The abstract should list principal alternative preventive , diagnostic , or therapeutic strategies available to targeted clinicians and patients . Outcomes The abstract also should specify which health outcomes , such as death , morbidity , quality of life , economic costs , or changes in the process of health care were considered . Evidence To estimate the probable effect of a health intervention on an outcome , relevant data must be defined , gathered , and appraised . Readers need to know what kind of evidence was considered and what methods were used to select and combine evidence from different sources . Potential sources of evidence about clinical outcomes include the results of clinical studies ( published or unpublished ) , expert opinion , information contained in public or private health data bases , and direct input from patients or providers . Potential sources of evidence about economic outcomes include the results of cost-effectiveness studies , various fee schedules , and information contained in public or private health cl aims data bases . Potential methods of gathering evidence include computerized search es for articles that satisfy predetermined criteria , review s of bibliographies of relevant articles , and surveys of relevant persons or organizations [ 1 ] . The abstract should state whether explicit methods were used to combine results from scientific studies ( for example , meta- analysis ) or opinions of experts ( for example , Delphi technique ) [ 14 , 15 ] . The abstract may also indicate whether specific criteria were used to gauge the quality of information from different sources [ 16 , 17 ] . Scientific evidence regarding the likelihood of certain outcomes is often missing or conflicting . It is desirable for the strength of evidence supporting a guideline to be gauged in some way [ 16 ] . If gaps in the evidence were bridged formally ( for example , through use of decision- analysis models ) or informally ( for example , best guess of clinical experts ) , then major assumptions or areas of uncertainty should be acknowledged [ 11 ] . Because of the extraordinary time required to properly assemble and review evidence and then to achieve consensus about practice recommendations , the abstract of a practice guideline should specify the publication date s of the most recent evidence considered . If a sensitivity analysis was performed , then any major vulnerability of the guideline to weaknesses in the evidence should be acknowledged . These considerations may be summarized by qualifying a guideline as provisional by specifying date s for expiration or review , by listing studies in progress that could affect the guideline , or by identifying key research priorities . Values The declaration of a recommended practice presumes an implicit or explicit process for judging the relative desirability of the health , economic , and process outcomes associated with alternative practice s. These are matters of opinion and value . For example , in developing guidelines for breast cancer screening , it is necessary to weigh the value of preventing a death from breast cancer against the value of avoiding unnecessary harm or anxiety in women who do not have breast cancer . A high value placed on maximizing detection of asymptomatic malignancy may motivate an organization to recommend teaching self-examination of breasts to young women [ 18 ] . A relatively greater value placed on avoiding false-positive results may motivate others to not promote such programs [ 19 ] . Consequently , the principal sources of such values and the method by which judgments were made should be reported in guideline abstract s. At a minimum , the abstract should identify the major groups that participated in the process of assigning values to outcomes ( for example , generalist or specialist physicians , other health care providers , insurers , representatives of health organizations , and special-interest groups ) and whether patient preferences were represented . The abstract may also indicate the method used to synthesize opinions from Introduction Women are largely unaware that mammography screening can cause overdetection of inconsequential disease , leading to overdiagnosis and overtreatment of breast cancer . Evidence is lacking about how information on overdetection affects women 's breast screening decisions and experiences . This study investigates the consequences of providing information about overdetection of breast cancer to women approaching the age of invitation to mammography screening . Methods and analysis This is a r and omised controlled trial with an embedded longitudinal qualitative sub study . Participants are a community sample of women aged 48–50 in New South Wales , Australia , recruited in 2014 . Women are r and omly allocated to either quantitative only follow-up ( n=904 ) or additional qualitative follow-up ( n=66 ) . Women in each stream are then r and omised to receive either the intervention ( evidence -based information booklet including overdetection , breast cancer mortality reduction and false positives ) or a control information booklet ( including mortality reduction and false positives only ) . The primary outcome is informed choice about breast screening ( adequate knowledge , and consistency between attitudes and intentions ) assessed via telephone interview at 2 weeks postintervention . Secondary outcomes measured at this time include decision process ( decisional conflict and confidence ) and psychosocial outcomes ( anticipated regret , anxiety , breast cancer worry and perceived risk ) . Women are further followed up at 6 months , 1 and 2 years to assess self-reported screening behaviour and long-term psychosocial outcomes ( decision regret , quality of life ) . Participants in the qualitative stream undergo additional in-depth interviews at each time point to explore the views and experiences of women who do and do not choose to have screening . Ethics and dissemination The study has ethical approval , and results will be published in peer- review ed journals . This research will help ensure that information about overdetection may be communicated clearly and effectively , using an evidence -based approach , to women considering breast cancer screening . Trial registration number Australian New Zeal and Clinical Trials Registry ACTRN12613001035718 Context Seven- and 10-year results of the Canadian National Breast Screening Study ( CNBSS ) showed no reduction in breast cancer mortality from five annual mammographies and breast examinations for 40- to 49-year-old women . Some authors have argued that longer follow-up would reveal important benefits . Contribution After 11 to 16 years , the cumulative rate ratios for mammography versus usual care were 0.97 ( 95 % CI , 0.74 to 1.27 ) for breast cancer mortality without adjustment for non study mammography and 1.06 ( CI , 0.80 to 1.40 ) with adjustment . Clinical Implication s The CNBSS suggests that screening 40- to 49-year-old women is unlikely to reduce breast cancer by 20 % or more . Controversy will persist because other studies suggest that screening causes small reductions in breast cancer mortality . The Editors The Canadian National Breast Screening Study -1 ( CNBSS-1 ) , an individually r and omized trial in women 40 to 49 years of age at study entry , evaluated the efficacy of annual mammography , breast physical examination , and instruction on breast self-examination in reducing breast cancer mortality  ( 1 ) . The 7-year ( 2 ) and preliminary 10-year ( 3 ) mortality results were previously reported . At 7 years , 38 women in the mammography group and 28 women in the usual care group had died of breast cancer , for a rate ratio of 1.36 ( 95 % CI , 0.84 to 2.21 ) ( 2 ) . At 10 years , there were 82 breast cancer deaths in the mammography group and 72 in the usual care group ( rate ratio , 1.14 [ CI , 0.83 to 1.56 ] ) ( 3 ) . This article reports CNBSS-1 results after an average 13-year follow-up from study entry . Methods Patient Selection and Recruitment Participants were recruited through media publicity , personal invitation letters using population lists ( municipal registers and provincial health insurance registers ) , group mailings , and physicians ( 4 ) . Eligibility criteria were age 40 to 49 years , no previous diagnosis of breast cancer , not being pregnant , no mammography in the previous 12 months , and signed informed consent . The Human Experimentation Committee of the University of Toronto ( Toronto , Ontario , Canada ) and Human Experimentation Committees at 15 CNBSS collaborating centers approved the study . A total of 50 430 women age 40 to 49 years were enrolled from January 1980 through March 1985 . R and omization Before r and omization , all participants received an initial breast physical examination and instruction on breast self-examination . They were then immediately r and omly assigned to receive mammography and , thereafter , either annual screening with mammography and breast physical examination ( 25 214 women in the mammography group were available for analysis ) or usual care in the context of the Canadian health care system ( 25 216 women in the usual care group were available for analysis ) . Center coordinators r and omly assigned participants using prepared allocation lists , independent of breast physical examination findings . This sequence ensured that the conduct and interpretation of the breast physical examination would be unbiased by knowledge of whether mammography would follow . Intervention Screening Schedule In the mammography group , 62 % of women received five annual screenings . The remainder , recruited later , received four . Each screening examination comprised mammography , breast physical examination , and instruction and evaluation on breast self-examination . Women in the mammography group completed question naires at each rescreening visit . Women in the usual care group were not recalled for rescreening but were mailed annual question naires . We expected that these participants would continue their normal pattern of medical care as delivered through Canada 's universal health care coverage , including access to mammography for diagnosis . Study Procedures Two-view mammography was done on dedicated mammography units ( 5 ) , and second readers review ed mammograms deemed abnormal . Systematic audit procedures were used ( 6 ) . Nurses provided breast physical examination in 12 centers and physicians in 3 centers in Qubec ( 7 ) . These providers taught and evaluated breast self-examination while conducting their own examination ( 8) . If findings on breast physical examination or mammography were abnormal , participants were referred to a CNBSS review clinic . The study surgeon discussed mammography findings with the study radiologist , examined the participant , and decided whether further diagnostic procedures should be recommended to the woman 's physician . The woman 's physician determined whether and how to implement the study surgeon 's recommendations . Data Collection Protocol During the screening period , the center coordinators collected surgery and pathology reports for breast-related diagnostic and therapeutic procedures . The CNBSS pathologists review ed all slides . If the community and CNBSS pathologist disagreed , a panel of three to five CNBSS pathologists blindedly and independently review ed the slides . Extensive quality control procedures were used during data collection . After the screening centers closed in 1988 , the central CNBSS central office annually followed all women known to have breast cancer until 30 June 1996 , the cut-off for this analysis . Passive follow-up of all participants through linkage with the National Cancer Registry identified new diagnoses of breast cancer in study participants through 31 December 1993 . The central office collected pathology reports for postscreening cases of breast cancer . The community diagnosis was accepted for study purpose s. Family members responding to the annual mailed question naire identified deaths that occurred before completion of a participant 's screening schedule . Thereafter , women not known to have cancer were followed only through registry linkage ; their mammography experience was not traced . However , for women known to have breast cancer , attending physicians received annual requests for up date d clinical information , including death .  Attending physicians , who received annual requests for information on women with breast cancer , reported deaths until 30 June 1996 . Linkage with the Canadian Mortality Data base at Statistics Canada ( including deaths in Canadians who resided in the United States at the time of death ) identified causes of death in the entire cohort until 31 December 1993 . The procedures used to verify deaths from breast cancer were described previously ( 2 ) . Investigative procedures were initiated for women dying with breast cancer ; those whose death certificates mentioned breast cancer ; and those whose cause of death was described as unknown , unknown primary , lung cancer , colon cancer , or liver cancer . The review ers were blinded to study group allocation . All other causes of death were accepted as certified . For the most recent record linkage , more stringent confidentiality requirements exercised by many hospitals hindered verification . Thus , of the breast cancer deaths reported in this paper , a panel review ed 67 % in the mammography group and 77 % in the usual care group . The remaining deaths are as reported on death certificates . Study Outcomes Death due to or probably due to breast cancer was the major study outcome . A previous report of the CNBBS-1 noted axillary node status , as assessed by community pathologists , through 7 years of follow-up ( 2 ) . Subsequently ( 1993 to 1997 ) , to achieve consistent reporting of tumor size , all available material for screening-detected cancer and cancer detected between screenings was re-collected from originating institutions and review ed by one of the CNBSS pathologists or a colleague . Slides were obtained for review for nearly 80 % of requested cases . For the current analysis , pathologists measured the size of small tumors as observed on the slide or the size of the invasive component for mixed invasive and in situ tumors . Statistical Analysis Sample Size The CNBSS-1 was planned to evaluate whether breast cancer mortality would decrease by 40 % in the  mammography group compared with the usual care group after 5 years of follow-up , with a required sample size of 50 000 women ( = 0.05 ; power , 80 % ) ( 1 ) . At 5 years , however , too few women had died of breast cancer for the study to achieve the planned power . Thus , for the first report on breast cancer mortality , we extended follow-up to 7 years ( 2 ) . CNBSS Data base The data base includes records for 50 430 women , including demographic and risk factor variables and results of screening examinations , diagnostic and therapeutic procedures , pathology results , and causes of death . CNBSS Terminology The terms screen 1 , screen 2 , through screen 5 denote events associated with screening examinations in the mammography group . The initial breast physical examination received by the usual care group is called screen 1 . Screening-detected cancers are those diagnosed after a recommendation made by the study surgeon at the CNBSS review clinic . Interval cancers are cases of cancer that occurred less than 12 months after a screening examination at which no recommendation for diagnostic procedures was made . Incident cancers are cases of cancer that occurred more than 12 months after the previous CNBSS screening examination . Statistical Tests The statistical significance of differences in proportions was determined by using the chi-square test ( two-sided = 0.05 ) . For all observed-to-expected ratios , 95 % CIs were computed . Death rates were computed by using person-years based on stratification by quinquennium of age ; we assumed that all women not known to be dead are alive . Age was defined as age at entry . Because all eligible participants were included in the analysis and follow-up , this is an intention-to-treat analysis . Cox proportional-hazards regression was done to examine variables with the most significant independent influence on survival ( 9 ) , using the PHREG program in SAS software , version 6.12 ( SAS Institute , Inc. , Cary , North Carolina ) . Because the variable allocation to screening was our primary interest , it was BACKGROUND Mammography screening can reduce breast cancer mortality . However , most women are unaware that inconsequential disease can also be detected by screening , leading to overdiagnosis and overtreatment . We aim ed to investigate whether including information about overdetection of breast cancer in a decision aid would help women aged around 50 years to make an informed choice about breast screening . METHODS We did a community-based , parallel-group , r and omised controlled trial in New South Wales , Australia , using a r and om cohort of women aged 48 - 50 years . Recruitment to the study was done by telephone ; women were eligible if they had not had mammography in the past 2 years and did not have a personal or strong family history of breast cancer . With a computer program , we r and omly assigned 879 participants to either the intervention decision aid ( comprising evidence -based explanatory and quantitative information on overdetection , breast cancer mortality reduction , and false positives ) or a control decision aid ( including information on breast cancer mortality reduction and false positives ) . Participants and interviewers were masked to group assignment . The primary outcome was informed choice ( defined as adequate knowledge and consistency between attitudes and screening intentions ) , which we assessed by telephone interview about 3 weeks after r and om allocation . The primary outcome was analysed in all women who completed the relevant follow-up interview questions fully . This trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12613001035718 . FINDINGS Between January , 2014 , and July , 2014 , 440 women were allocated to the intervention group and 439 were assigned to the control group . 21 women in the intervention group and 20 controls were lost to follow-up ; a further ten women assigned to the intervention and 11 controls did not answer all questions on attitudes . Therefore , 409 women in the intervention group and 408 controls were analysed for the primary outcome . 99 ( 24 % ) of 409 women in the intervention group made an informed choice compared with 63 ( 15 % ) of 408 in the control group ( difference 9 % , 95 % CI 3 - 14 ; p=0·0017 ) . Compared with controls , more women in the intervention group met the threshold for adequate overall knowledge ( 122/419 [ 29 % ] vs 71/419 [ 17 % ] ; difference 12 % , 95 % CI 6 - 18 ; p<0·0001 ) , fewer women expressed positive attitudes towards screening ( 282/409 [ 69 % ] vs 340/408 [ 83 % ] ; 14 % , 9 - 20 ; p<0·0001 ) , and fewer women intended to be screened ( 308/419 [ 74 % ] vs 363/419 [ 87 % ] ; 13 % , 8 - 19 ; p<0·0001 ) . When conceptual knowledge alone was considered , 203 ( 50 % ) of 409 women in the intervention group made an informed choice compared with 79 ( 19 % ) of 408 in the control group ( p<0·0001 ) . INTERPRETATION Information on overdetection of breast cancer provided within a decision aid increased the number of women making an informed choice about breast screening . Becoming better informed might mean women are less likely to choose screening . FUNDING Australian National Health and Medical Research Council This prospect i ve study examined whether the psychological impact of organized mammography screening is influenced by women 's pre-existing experience with breast cancer and perceived susceptibility ( PS ) to the disease . From a target population of 16,886 , a r and om sample of women with a normal screening finding and all women with a false positive or a benign biopsy finding were included ( N=1942 ) . Data were collected with postal question naires 1-month before screening invitation and 2 and 12 months after screening . Response rate was 63 % at baseline ; 86 , and 80 % of the baseline participants responded to the follow-ups . Psychological impact was measured as anxiety ( STAI-S ) , depression ( BDI ) , health-related concerns ( IAS ) , and breast cancer-specific beliefs and concerns . Data was analyzed with repeated measures analyses of variance , with estimates of effect size based on Eta-squared . Women with breast cancer experience had higher risk perception already before screening invitation ; after screening they were also more distressed . Women with high PS were more distressed than women with low PS also at pre-invitation . The distress was not alleviated by screening , but instead remained even after normal mammograms . Experience and PS did not influence responses to different screening findings . Of the finding groups , false positives experienced most adverse effects : their risk perception increased and they reported most post-screening breast cancer-specific concerns . Furthermore , they became more frequent in breast self-examination ( BSE ) despite a simultaneous decrease in BSE self-efficacy . Our findings suggest that women with high PS and women with false positive screening finding may need individualized counseling and follow-up as much as women with a family history of breast cancer . Besides medical risk factors , women 's own perceptions of susceptibility should be discussed during the screening process PURPOSE / OBJECTIVES To assess the efficacy of  Korean Immigrants and Mammography-Culture-Specific Health Intervention ( KIM-CHI ) , an educational program for Korean American ( KA ) couples design ed to improve  mammography uptake among KA women . DESIGN A two-group cluster r and omized , longitudinal , controlled design . SETTING 50 KA religious organizations in the Chicago area . SAMPLE 428 married KA women 40 years of age or older who had not had a mammogram in the past year . The women and their husb and s were recruited from 50 KA religious organizations . METHODS Couples were r and omly assigned to intervention or attention control groups . Those in the KIM-CHI program ( n = 211 couples ) were compared to an attention control group ( n = 217 couples ) at baseline , as well as at 6 and 15 months postintervention on mammogram uptake . MAIN RESEARCH VARIABLES Sociodemographic variables and mammography uptake were measured . Level of acculturation was measured using the Suinn-Lew Asian Self-Identity Acculturation Scale . Research ers asked questions about healthcare re sources and use , health insurance status , usual source of care , physical examinations in the past two years , family history of breast cancer , and history of mammography . FINDINGS The KIM-CHI group showed statistically significant increases in mammography uptake compared to the attention control group at 6 months and 15 months postintervention . CONCLUSIONS The culturally targeted KIM-CHI program was effective in increasing mammogram uptake among nonadherent KA women . IMPLICATION S FOR NURSING Nurses and healthcare providers should consider specific health beliefs as well as inclusion of husb and s or significant others . They also should target education to be culturally relevant for KA women to effectively improve frequency of breast cancer screening It is the responsibility of the scientist to balance passion with dispassion . John C. Polanyi The Responsibility of the Scientist Department of Physiology Lecture Series : Frontiers in Physiology and Pharmacology , University of Toronto , 22 M Because no previous study evaluating the benefit of screening for breast cancer had specifically addressed efficacy in women aged 40 to 49 years , the results of the Canadian National Breast Screening Study ( NBSS ) were impatiently awaited . When they were finally published in November 1992 [ 1 , 2 ] , the results showed no reduction in breast cancer mortality after 7 years in screened women aged 40 to 49 years . Further , mammography did not achieve an incremental mortality benefit over and above clinical examination in women 50 to 59 years old , although it did achieve higher rates of cancer detection . What one wants to believe is easy to believe . Results from the NBSS , however , were difficult for many to believe . Given the passionately held belief that early detection of breast cancer achieved by mammography screening benefits women aged 40 to 49 years , it was not surprising that the NBSS became the focus of much attention . Some of the criticisms that have been generated are addressed in this article in the hope that a better underst and ing of the issues involved will be reached . Methods Planned in the late 1970s , the NBSS began screening women in January 1980 . Its design [ 3 ] addressed the unanswered questions prevailing at the time . The New York Health Insurance Plan breast screening trial had shown that combined annual screening with mammography and physical examination reduced breast cancer mortality in women 50 years of age and over when compared with no screening [ 4 ] . Although the separate contributions of mammography and physical examination of the breasts to mortality reduction were not known , it was believed that clinical examination of the breasts made a major contribution . Also not known in 1980 was whether combined annual screening  reduced breast cancer mortality in women aged 40 to 49 years when compared with no screening intervention . To determine the benefit of combined screening in women aged 40 to 49 years , the NBSS recruited 50 430 women individually r and omly assigned so that 25 214 received annual mammography and physical examination and 25 216 received a single physical examination  , thereafter returning to usual community care with annual follow-up by mailed question naire . To determine the separate contribution of mammography to breast cancer mortality reduction , 39 405 women ages 50 to 59 years were recruited , of whom 19 711 were r and omly assigned to receive annual mammography and physical examination of the breasts and 19 694 to receive an  annual physical examination alone . Entry criteria included meeting the age criteria , not being pregnant , not having been diagnosed with breast cancer , not having had a mammogram in the 12 months before entry , and signing informed consent forms . Women were instructed in breast self-examination at entry and those eligible for re-screening received repeated instruction and evaluation . All su bmi tted annual question naires that tracked breast procedures generated outside the NBSS . Screening Sites Each of the 15 centers across Canada had an adequate population base from which to draw participants and had recognized expertise in breast cancer . Six centers were in provincial cancer institutions ( all in the forefront of cancer research and treatment ) and eight in university teaching hospitals . Recruitment extended over 6 years , from 1980 to 1985 . R and omization Women who met the entry criteria and completed two question naires ( yielding identifying and demographic data including risk factors for breast cancer ) then signed informed consent forms in the examining room . The screen-examiner asked if the participant had breast symptoms ( lump , pain , discharge ) and recorded the responses . A physical examination of the breasts and instruction in breast self-examination followed , after which the examiner decided if the clinical findings required the participant 's referral to the NBSS surgical review clinic ( usually held within 1 week ) . This decision was documented on the examiner 's form , and the woman was informed . The examiner then left the participant and approached the center coordinator or her deputy , who carried out the r and omization procedure . R and omization lists , contained in four separate books that each included one quinquennium ( 40 to 44 years , 45 to 49 years , and so on ) , were provided to all centers . On learning the participant 's age , the coordinator chose the appropriate book and entered the date and name on the first available line , thus assigning to the participant her identification number and allocation . The coordinator entered the number and allocation on all chart forms , and the examiner told the participant if she was to have mammography . From the examiner 's perspective , it was not important to obtain a mammography allocation if a breast lump had been found because the participant would already be referred for surgical review . From the coordinator 's perspective , skipping a line to achieve a desired allocation was not feasible because she could not predict when the next appropriately aged woman would arrive to fill the skipped slot . The coordinators were well educated , well trained , and responsible , and recognized the importance of the r and omization procedure . At each month 's end , the original r and omization sheets were su bmi tted to the central coordinating office where each sheet was examined for suspicious entries , inappropriate date s , and lack of congruence with participant records . Mammography Mammography was done on site and interpreted by study radiologists . Details of the equipment used , the audit procedures , and sensitivity and specificity estimates have been previously published [ 5 - 7 ] . Clinical Examination of the Breasts Breast examination and breast self-examination instruction and evaluation were done by locally trained nurse-examiners in all centers outside the province of Quebec and by physicians in Quebec . The duration of the clinical examination ranged from 5 to 15 minutes , depending on the size of the breasts and on the amount of verbal interaction required . Descriptions of the role of the nurse-examiner , sensitivity and specificity estimates for breast examination , and breast self-examination behavior have all been previously published [ 8 - 10 ] . Surgical Review Study surgeons appointed at each center to examine women with abnormalities detected by either or both screening  interventions  decided if diagnostic follow-up was required . If so , they forwarded their recommendations to the woman 's physician , who then determined if and where the procedure would be done . Most recommended procedures were done [ 1 , 2 ] . In women aged 40 to 49 years , diagnostic mammography was done as a consequence of the screening examination in 0.8 % and 1.5 % of the mammography and comparison groups , respectively . Pathology Review Reference pathologists appointed for each center review ed slides from all surgical procedures done on participants from their center , whether or not the procedure result ed from NBSS recommendations . Follow-up Procedures During the 3 or 4 years each participant was in the study ( participants entering in 1984 and 1985 were eligible for only a 3-year and four-screen schedule ) , the centers ' routine follow-up procedures ensured high compliance with screening , and question naire information was obtained for most of the noncompliant participants [ 1 , 2 ] . These procedures also achieved almost complete ascertainment of cases of breast cancer and deaths , shown by subsequent record linkage . After participants ' screening schedules ended , active follow-up continued only for participants with known breast cancer . All such patients have always been and continue to be followed annually through contact with their physicians , whether their breast cancers were detected as a result of screening , during the screening schedule but not as a result of screening , or through record linkage during or after screening . Thus , the vital status of all women identified as having breast cancer is ascertained within , at most , 1 year of death . Passive follow-up to identify new cases of breast cancer through linkage with cancer registries across Canada ascertained breast cancer diagnoses occurring after completion of screening schedules and in the very small proportion of women ( 1 % of women from 40 to 49 years ) who dropped out of the study before completing their schedule . In a few cases , breast cancer was first identified through the National Mortality Data base as a cause of , or contributing to , death . In such cases , surgical , pathology , and other clinical records were review ed retrospectively . Figure 1 shows the follow-up procedures . Figure 1 . Flow chart of follow-up procedures . Results Seven years after entry , breast screening had no effect on breast cancer deaths when women aged 40 to 49 years receiving annual screening with mammography and physical examination  ( 38 deaths ) were compared with women receiving only a single physical examination of the breasts at entry into the  study followed by usual community care ( 28 deaths ) . The numeric difference is not statistically significant . Further , no effect on breast cancer mortality was observed in women aged 50 to 59 years at entry who received annual mammography and physical examination of the breasts ( 38 deaths ) compared with women who received only annual physical examination of the breasts ( 39 deaths ) . In both age groups , mammography was associated with higher cancer detection rates [ 1 , 2 ] . Controversy When the results were published , controversy arose [ 11 - 13 ] , some of which was defused at a recent International Workshop on Breast Cancer Screening where it was observed that NBSS results were consistent with findings from other screening studies [ 14 ] . Nevertheless , NBSS results were unwelcome in a milieu Objective To obtain quality -of-life ( QOL ) valuations associated with mammography screening and breast cancer treatment that are suitable for use in cost-effectiveness analyses . Methods Subjects comprised 131 women ( age range 50–79 years ) r and omly sample d from a breast cancer screening program .  In an in-person or telephone interview , women rated the QOL impact of 14 clinical scenarios ( ranging from mammography to end-of-life care for breast cancer ) using a visual analogue scale anchored by death ( 0 ) and perfect health/ quality of life ( 100 ) . Results Women rated the scenarios describing true negative results , false positive results , and routine screening mammography at 80 or above on a scale of 0–100 , suggesting that they perceive these states as being close to perfect health . They rated  adjuvant chemotherapy  ( 39.7 ; range 10–90 ) , palliation/end-of-life care ( 35.8 ; range 0–100 ) , and recurrence at 1 year ( 33.0 ; range 0–95 ) the lowest , suggesting that these health states are perceived as compromised . Women rated receiving news of a breast cancer diagnosis ( true positive ) ( 45.7 ; range 5–100 ) and receiving delayed news of a breast cancer diagnosis ( false negative ) ( 48.5 ; range 5–100 ) as being comparable to undergoing mastectomy ( 48.3 ; range 10–100 ) and radiation therapy ( 46.2 ; range 5–100 ) for breast cancer . Conclusions These data can be used to up date cost analyses of mammography screening that wish to take into account the QOL impact of screening Background Although guidelines recommend that clinicians consider life expectancy before screening older women for breast cancer , many older women with limited life expectancies are screened . We aim ed to identify factors important to mammography screening decisions among women aged 80 and older compared to women aged 65–79 . Methods Telephone surveys of 107 women aged 80 + and 93 women aged 65–79 r and omly selected from one academic primary care practice who were able to communicate in English ( 60 % response rate ) . The survey addressed the following factors in regards to older women 's mammography screening decisions : perceived importance of a history of breast disease , family history of breast cancer , doctor 's recommendations , habit , reassurance , previous experience , mailed reminder cards , family/friend 's recommendations or experience with breast cancer , age , health , and media . The survey also assessed older women 's preferred role in decision making around mammography screening . Results Of the 200 women , 65.5 % were non-Hispanic white and 82.8 % were in good to excellent health . Most ( 81.3 % ) had undergone mammography in the past 2 years . Regardless of age , older women ranked doctor 's recommendations as the most important factor influencing their decision to get screened . Habit and reassurance were the next two highly ranked factors influencing older women to get screened . Among women who did not get screened , women aged 80 and older ranked age and doctor 's counseling as the most influential factors and women aged 65–79 ranked a previous negative experience with mammography as the most important factor . There were no significant differences in preferred role in decision-making around mammography screening by age , however , most women in both age groups preferred to make the final decision on their own ( 46.6 % of women aged 80 + and 50.5 % of women aged 65–79 ) . Conclusion While a doctor 's recommendation is the most important factor influencing elderly women 's mammography screening decisions , habit and reassurance also strongly influence decision-making . Interventions aim ed at improving clinician counseling about mammography , which include discussion s around habit and reassurance , may result in better decision-making The study aim ed to assess associations between Health Belief Model variables , stages of change , and participation in mammography for early detection of breast cancer in a sample of Iranian women . A total of 414 women , aged 40 to 73 years , were recruited by r and om sampling . The study took place in the winter of 2007 , using a self-report question naire and structured interviews , design ed to measure the five Health Belief Model constructs and stages of adoption for mammography . The study indicated that 45.8 % of the women were in the pre-contemplation and contemplation stages of a mammogram , and 29 % of participants reported having had at least one mammogram . Screening behavior was associated with older age , familial history of breast cancer , history of breast disease , health insurance coverage , and living in an urban area . Furthermore , the perceived susceptibility to breast cancer , perceived benefits and barriers for mammography , and cues to action variables defined by the Health Belief Model were four factors related to having a mammogram . The study concludes that health care professionals must provide women with more fear appeals that outline vulnerability to developing breast cancer , remove cognitive barriers to seeking mammography , and apply effective guidance on the participation of women in breast cancer screening programs BACKGROUND To reduce breast cancer mortality , ways to promote the use of mammography screening among women age 50 and above are needed . Community organization may be a useful approach . METHODS The Washington State Community Breast Cancer Screening Project involved implementation of promotional activities initiated by physician and lay community boards in two communities . Two comparable communities served as controls for evaluation purpose s. R and om-digit-dial telephone interviews were used to assess recent use of mammography  at baseline and follow-up in independent sample s of women ages 50 to 75 from the four communities . The extent of exposure to intervention activities and the relationship between exposure to intervention activities and mammography use were estimated from data collected at follow-up . RESULTS Exposure to patient reminders from physicians , wallet reminder cards , and newspaper advertisements were consistently related to mammography use . Physician office staff encouragement and a display board were significantly related to mammography use only in Intervention Communities A and B , respectively . Neither exposure to promotional activities nor the change in prevalence of mammography use was significantly higher in the intervention communities than in the comparison communities at follow-up . CONCLUSIONS Although several activities were useful in promoting mammography use , organization of the community did not enhance efforts undertaken spontaneously by comparable communities BACKGROUND False-positive mammography results are common . Biennial screening may decrease the cumulative probability of false-positive results across many years of repeated screening but could also delay cancer diagnosis . OBJECTIVE To compare the cumulative probability of false-positive results and the stage distribution of incident breast cancer after 10 years of annual or biennial screening mammography . DESIGN Prospect i ve cohort study . SETTING 7 mammography registries in the National Cancer Institute-funded Breast Cancer Surveillance Consortium . PARTICIPANTS 169,456 women who underwent first screening mammography at age 40 to 59 years between 1994 and 2006 and 4492 women with incident invasive breast cancer diagnosed between 1996 and 2006 . MEASUREMENTS False-positive recalls and biopsy recommendations stage distribution of incident breast cancer . RESULTS False-positive recall probability was 16.3 % at first and 9.6 % at subsequent mammography . Probability of false-positive biopsy recommendation was 2.5 % at first and 1.0 % at subsequent examinations . Availability of comparison mammograms halved the odds of a false-positive recall ( adjusted odds ratio , 0.50 [ 95 % CI , 0.45 to 0.56 ] ) . When screening began at age 40 years , the cumulative probability of a woman receiving at least 1 false-positive recall after 10 years was 61.3 % ( CI , 59.4 % to 63.1 % ) with annual and 41.6 % ( CI , 40.6 % to 42.5 % ) with biennial screening . Cumulative probability of false-positive biopsy recommendation was 7.0 % ( CI , 6.1 % to 7.8 % ) with annual and 4.8 % ( CI , 4.4 % to 5.2 % ) with biennial screening . Estimates were similar when screening began at age 50 years . A non-statistically significant increase in the proportion of late-stage cancers was observed with biennial compared with annual screening ( absolute increases , 3.3 percentage points [ CI , -1.1 to 7.8 percentage points ] for women age 40 to 49 years and 2.3 percentage points [ CI , -1.0 to 5.7 percentage points ] for women age 50 to 59 years ) among women with incident breast cancer . LIMITATIONS Few women underwent screening over the entire 10-year period . Radiologist characteristics influence recall rates and were unavailable . Most mammograms were film rather than digital . Incident cancer was analyzed in a small sample of women who developed cancer . CONCLUSION After 10 years of annual screening , more than half of women will receive at least 1 false-positive recall , and 7 % to 9 % will receive a false-positive biopsy recommendation . Biennial screening appears to reduce the cumulative probability of false-positive results after 10 years but may be associated with a small absolute increase in the probability of late-stage cancer diagnosis . PRIMARY FUNDING SOURCE National Cancer Institute Breast cancer screening programs have been initiated in many countries in the past decade . To determine the impact of the Screening Mammography Program of British Columbia ( SMPBC ) , disease and treatment outcomes for women with breast cancer diagnosed in BC between 1989 and 1996 were compared on the basis of attendance at the SMPBC . An SMPBC attender was a women diagnosed with breast cancer within three years of an SMPBC screen , regardless whether the cancer was detected as a result of that screen . Of the 13,636 women aged 40–89 years diagnosed with breast cancer in BC during the study period , 2,647 ( 19.4 % ) were SMPBC attenders . 73.5 % of SMPBC attenders ( N=1,946 ) and 74.2 % of non-attenders ( N=8,149 ) were referred to the BC Cancer Agency and had pathology , staging , treatment , and outcome information available . SMPBC attenders compared with non-attenders were more likely to have in situ disease alone , and those with invasive cancers had smaller tumors which were less likely to have grade III histology and less likely to have spread to axillary lymph nodes ( all P<0.001 ) . SMPBC attenders were more likely to be treated with breast conservation and less likely to receive adjuvant chemotherapy or tamoxifen  ( P < 0.001 ) . Log-rank tests showed local ( P = 0.017 ) , distant ( P < 0.001 ) , and overall ( P < 0.001 ) disease-free survival were better for SMPBC attenders . These favorable surrogate endpoints suggest that the benefits of breast screening as demonstrated by r and omized trials can be translated into community practice by an organized breast screening program
For example , mammography screening does not seem to create anxiety in women who are given a clear result after a mammogram .
The incidence of breast cancer and mortality increases with age , and the GDG extrapolated that the absolute health benefits are greater in women aged 45 to 49 than those aged 40 to 44 years .
However , for the 45- to 49-year age group , the higher breast cancer incidence and mortality compared with women between the ages of 40 and 44 , as well as observational evidence showing a greater benefit in this age group ( 33 ) , led the GDG to judge that the balance of health effects probably favors screening , although the required re sources for screening likely differ across setting s ( 34 , 35 ) .
Other EtD criteria also were generally in favor of implementing organized mammography screening in this age group .
Despite intensified efforts by the European Council since 2003 , the implementation of organized , population -based mammography screening is not uniform across Europe and depends greatly on the policies in place in different countries , the organization of health care , and available re sources ( 1 ) .
Since the last edition of the European Guidelines on Breast Cancer Screening and Diagnosis was published in 2006 ( 2 ) , new evidence regarding breast cancer and innovation in guideline methodology prompted the European Commission Initiative on Breast Cancer ( ECIBC ) to develop new evidence -based recommendations ( in short , the European Breast Guidelines ) .
These guidelines inform women , health professionals , and policymakers about important questions related to organized mammography screening and breast cancer diagnosis , but recommendations may apply in context s in which organized screening programs are not in place .
Women generally consider these undesirable effects acceptable ( low certainty of evidence ) , and a systematic review suggested that women place a relatively low value on the psychosocial and physical effects of false-positive results and overdiagnosis ; however , some studies raised concerns about whether women fully underst and the result ing implication s ( 15 ) .
How Often Should Women Attend an Organized Mammography Screening Program ?