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      Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis

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          Abstract

          Background

          Mammography is less effective in detecting cancer in dense than in fatty breasts.

          Methods

          We undertook a systematic search in PubMed to identify studies on women with dense breasts who underwent screening with mammography supplemented with ultrasound. A meta-analysis was undertaken on the proportion of cancers detected only by ultrasound, out of all screen-detected cancers, and the proportion of women with negative mammography who were referred for assessment following ultrasound screening.

          Results

          Twenty-nine studies satisfied our inclusion criteria. The proportion of total cancers detected only by ultrasound was 0.29 (95% CI: 0.27–0.31), consistent with an approximately 40% increase in the detection of cancers compared to mammography. In the studied populations, this translated into an additional 3.8 (95% CI: 3.4–4.2) screen-detected cases per 1000 mammography-negative women. About 13% (32/248) of cancers were in situ from 17 studies with information on this subgroup. Ultrasound approximately doubled the referral for assessment in three studies with these data.

          Conclusions

          Studies have consistently shown an increased detection of breast cancer by supplementary ultrasound screening. An inclusion of supplementary ultrasound into routine screening will need to consider the availability of ultrasound and diagnostic assessment capacities.

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          Most cited references45

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          Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers.

          Screening mammography is the best method to reduce mortality from breast cancer, yet some breast cancers cannot be detected by mammography. Cancers diagnosed after a negative mammogram are known as interval cancers. This study investigated whether mammographic breast density is related to the risk of interval cancer. Subjects were selected from women participating in mammographic screening from 1988 through 1993 in a large health maintenance organization based in Seattle, WA. Women were eligible for the study if they had been diagnosed with a first primary invasive breast cancer within 24 months of a screening mammogram and before a subsequent one. Interval cancer case subjects (n = 149) were women whose breast cancer occurred after a negative or benign mammographic assessment. Screen-detected control subjects (n = 388) were diagnosed after a positive screening mammogram. One radiologist, who was blinded to cancer status, assessed breast density by use of the American College of Radiology Breast Imaging Reporting and Data System. Mammographic sensitivity (i.e., the ability of mammography to detect a cancer) was 80% among women with predominantly fatty breasts but just 30% in women with extremely dense breasts. The odds ratio (OR) for interval cancer among women with extremely dense breasts was 6.14 (95% confidence interval [CI] = 1.95-19.4), compared with women with extremely fatty breasts, after adjustment for age at index mammogram, menopausal status, use of hormone replacement therapy, and body mass index. When only those interval cancer cases confirmed by retrospective review of index mammograms were considered, the OR increased to 9.47 (95% CI = 2.78-32.3). Mammographic breast density appears to be a major risk factor for interval cancer.
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            Prevalence of mammographically dense breasts in the United States.

            National legislation is under consideration that would require women with mammographically dense breasts to be informed of their breast density and encouraged to discuss supplemental breast cancer screening with their health care providers. The number of US women potentially affected by this legislation is unknown.
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              Overdiagnosis in mammographic screening for breast cancer in Europe: a literature review.

              Overdiagnosis, the detection through screening of a breast cancer that would never have been identified in the lifetime of the woman, is an adverse outcome of screening. We aimed to determine an estimate range for overdiagnosis of breast cancer in European mammographic service screening programmes. We conducted a literature review of observational studies that provided estimates of breast cancer overdiagnosis in European population-based mammographic screening programmes. Studies were classified according to the presence and the type of adjustment for breast cancer risk (data, model and covariates used), and for lead time (statistical adjustment or compensatory drop). We expressed estimates of overdiagnosis from each study as a percentage of the expected incidence in the absence of screening, even if the variability in the age range of the denominator could not be removed. Estimates including carcinoma in situ were considered when available. There were 13 primary studies reporting 16 estimates of overdiagnosis in seven European countries (the Netherlands, Italy, Norway, Sweden, Denmark, UK and Spain). Unadjusted estimates ranged from 0% to 54%. Reported estimates adjusted for breast cancer risk and lead time were 2.8% in the Netherlands, 4.6% and 1.0% in Italy, 7.0% in Denmark and 10% and 3.3% in England and Wales. The most plausible estimates of overdiagnosis range from 1% to 10%. Substantially higher estimates of overdiagnosis reported in the literature are due to the lack of adjustment for breast cancer risk and/or lead time.
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                Author and article information

                Contributors
                s.w.duffy@qmul.ac.uk
                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group UK (London )
                0007-0920
                1532-1827
                8 May 2018
                8 May 2018
                June 2018
                : 118
                : 12
                : 1559-1570
                Affiliations
                [1 ]ISNI 0000 0001 2171 1133, GRID grid.4868.2, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts & The London School of Medicine and Dentistry, , Queen Mary University of London, ; Charterhouse Square, London, EC1M 6BQ UK
                [2 ]ISNI 0000 0004 1936 7988, GRID grid.4305.2, Edinburgh Clinical Trials Unit, Usher Institute of Population Health Sciences and Informatics, , University of Edinburgh, ; Edinburgh, UK
                Author information
                http://orcid.org/0000-0001-9597-645X
                Article
                80
                10.1038/s41416-018-0080-3
                6008336
                29736009
                e8ce9620-4b52-4d4f-b3fc-732e5c5c4a2e
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 December 2017
                : 7 March 2018
                : 19 March 2018
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                © Cancer Research UK 2018

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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