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      Benefits and harms of mammography screening

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          Abstract

          Mammography screening for breast cancer is widely available in many countries. Initially praised as a universal achievement to improve women's health and to reduce the burden of breast cancer, the benefits and harms of mammography screening have been debated heatedly in the past years. This review discusses the benefits and harms of mammography screening in light of findings from randomized trials and from more recent observational studies performed in the era of modern diagnostics and treatment. The main benefit of mammography screening is reduction of breast-cancer related death. Relative reductions vary from about 15 to 25% in randomized trials to more recent estimates of 13 to 17% in meta-analyses of observational studies. Using UK population data of 2007, for 1,000 women invited to biennial mammography screening for 20 years from age 50, 2 to 3 women are prevented from dying of breast cancer. All-cause mortality is unchanged. Overdiagnosis of breast cancer is the main harm of mammography screening. Based on recent estimates from the United States, the relative amount of overdiagnosis (including ductal carcinoma in situ and invasive cancer) is 31%. This results in 15 women overdiagnosed for every 1,000 women invited to biennial mammography screening for 20 years from age 50. Women should be unpassionately informed about the benefits and harms of mammography screening using absolute effect sizes in a comprehensible fashion. In an era of limited health care resources, screening services need to be scrutinized and compared with each other with regard to effectiveness, cost-effectiveness and harms.

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          Screening for breast cancer with mammography

          A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published and national policies vary. To assess the effect of screening for breast cancer with mammography on mortality and morbidity. We searched PubMed (22 November 2012) and the World Health Organization's International Clinical Trials Registry Platform (22 November 2012). Randomised trials comparing mammographic screening with no mammographic screening. Two authors independently extracted data. Study authors were contacted for additional information. Eight eligible trials were identified. We excluded a trial because the randomisation had failed to produce comparable groups.The eligible trials included 600,000 women in the analyses in the age range 39 to 74 years. Three trials with adequate randomisation did not show a statistically significant reduction in breast cancer mortality at 13 years (relative risk (RR) 0.90, 95% confidence interval (CI) 0.79 to 1.02); four trials with suboptimal randomisation showed a significant reduction in breast cancer mortality with an RR of 0.75 (95% CI 0.67 to 0.83). The RR for all seven trials combined was 0.81 (95% CI 0.74 to 0.87). We found that breast cancer mortality was an unreliable outcome that was biased in favour of screening, mainly because of differential misclassification of cause of death. The trials with adequate randomisation did not find an effect of screening on total cancer mortality, including breast cancer, after 10 years (RR 1.02, 95% CI 0.95 to 1.10) or on all-cause mortality after 13 years (RR 0.99, 95% CI 0.95 to 1.03).Total numbers of lumpectomies and mastectomies were significantly larger in the screened groups (RR 1.31, 95% CI 1.22 to 1.42), as were number of mastectomies (RR 1.20, 95% CI 1.08 to 1.32). The use of radiotherapy was similarly increased whereas there was no difference in the use of chemotherapy (data available in only two trials). If we assume that screening reduces breast cancer mortality by 15% and that overdiagnosis and overtreatment is at 30%, it means that for every 2000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings. To help ensure that the women are fully informed before they decide whether or not to attend screening, we have written an evidence-based leaflet for lay people that is available in several languages on www.cochrane.dk. Because of substantial advances in treatment and greater breast cancer awareness since the trials were carried out, it is likely that the absolute effect of screening today is smaller than in the trials. Recent observational studies show more overdiagnosis than in the trials and very little or no reduction in the incidence of advanced cancers with screening.
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            Screening for breast cancer: an update for the U.S. Preventive Services Task Force.

            This systematic review is an update of evidence since the 2002 U.S. Preventive Services Task Force recommendation on breast cancer screening. To determine the effectiveness of mammography screening in decreasing breast cancer mortality among average-risk women aged 40 to 49 years and 70 years or older, the effectiveness of clinical breast examination and breast self-examination, and the harms of screening. Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the fourth quarter of 2008), MEDLINE (January 2001 to December 2008), reference lists, and Web of Science searches for published studies and Breast Cancer Surveillance Consortium for screening mammography data. Randomized, controlled trials with breast cancer mortality outcomes for screening effectiveness, and studies of various designs and multiple data sources for harms. Relevant data were abstracted, and study quality was rated by using established criteria. Mammography screening reduces breast cancer mortality by 15% for women aged 39 to 49 years (relative risk, 0.85 [95% credible interval, 0.75 to 0.96]; 8 trials). Data are lacking for women aged 70 years or older. Radiation exposure from mammography is low. Patient adverse experiences are common and transient and do not affect screening practices. Estimates of overdiagnosis vary from 1% to 10%. Younger women have more false-positive mammography results and additional imaging but fewer biopsies than older women. Trials of clinical breast examination are ongoing; trials for breast self-examination showed no reductions in mortality but increases in benign biopsy results. Studies of older women, digital mammography, and magnetic resonance imaging are lacking. Mammography screening reduces breast cancer mortality for women aged 39 to 69 years; data are insufficient for older women. False-positive mammography results and additional imaging are common. No benefit has been shown for clinical breast examination or breast self-examination.
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              Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial

              Objective To compare breast cancer incidence and mortality up to 25 years in women aged 40-59 who did or did not undergo mammography screening. Design Follow-up of randomised screening trial by centre coordinators, the study’s central office, and linkage to cancer registries and vital statistics databases. Setting 15 screening centres in six Canadian provinces,1980-85 (Nova Scotia, Quebec, Ontario, Manitoba, Alberta, and British Columbia). Participants 89 835 women, aged 40-59, randomly assigned to mammography (five annual mammography screens) or control (no mammography). Interventions Women aged 40-49 in the mammography arm and all women aged 50-59 in both arms received annual physical breast examinations. Women aged 40-49 in the control arm received a single examination followed by usual care in the community. Main outcome measure Deaths from breast cancer. Results During the five year screening period, 666 invasive breast cancers were diagnosed in the mammography arm (n=44 925 participants) and 524 in the controls (n=44 910), and of these, 180 women in the mammography arm and 171 women in the control arm died of breast cancer during the 25 year follow-up period. The overall hazard ratio for death from breast cancer diagnosed during the screening period associated with mammography was 1.05 (95% confidence interval 0.85 to 1.30). The findings for women aged 40-49 and 50-59 were almost identical. During the entire study period, 3250 women in the mammography arm and 3133 in the control arm had a diagnosis of breast cancer, and 500 and 505, respectively, died of breast cancer. Thus the cumulative mortality from breast cancer was similar between women in the mammography arm and in the control arm (hazard ratio 0.99, 95% confidence interval 0.88 to 1.12). After 15 years of follow-up a residual excess of 106 cancers was observed in the mammography arm, attributable to over-diagnosis. Conclusion Annual mammography in women aged 40-59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available. Overall, 22% (106/484) of screen detected invasive breast cancers were over-diagnosed, representing one over-diagnosed breast cancer for every 424 women who received mammography screening in the trial.
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                Author and article information

                Contributors
                magnus.loberg@medisin.uio.no
                mette.lise.lousdal@publ.au.dk
                micahel.bretthauer@medisin.uio.no
                mkalager@hsph.harvard.edu
                Journal
                Breast Cancer Res
                Breast Cancer Research : BCR
                BioMed Central (London )
                1465-5411
                1465-542X
                1 May 2015
                1 May 2015
                2015
                : 17
                : 1
                : 63
                Affiliations
                [ ]Institute of Health and Society, University of Oslo, N-0317 Oslo, Norway
                [ ]Department of Transplantation Medicine, Oslo University Hospital, 0424 Oslo, Norway
                [ ]Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115 USA
                [ ]Department of Public Health, Aarhus University, 8000 Aarhus C, Denmark
                [ ]Department of Medicine, Sorlandet Hospital, 4604 Kristiansand, Norway
                [ ]Telemark Hospital, 3710 Skien, Norway
                Article
                525
                10.1186/s13058-015-0525-z
                4415291
                25928287
                ccd14513-aa01-430f-89ce-9e7a28775e16
                © Løberg et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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                © The Author(s) 2015

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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