Overdiagnosis in screening mammography in Denmark: Population based cohort study

Department of Public Health, University of Copenhagen, Østre Farimagsgade 5, DK 1014 Copenhagen K, Denmark.
BMJ (online) (Impact Factor: 17.45). 02/2013; 346(feb26 1):f1064. DOI: 10.1136/bmj.f1064
Source: PubMed


To use data from two longstanding, population based screening programmes to study overdiagnosis in screening mammography.
Population based cohort study.
Copenhagen municipality (from 1991) and Funen County (from 1993), Denmark.
57 763 women targeted by organised screening, aged 56-69 when the screening programmes started, and followed up to 2009.
Overdiagnosis of breast cancer in women targeted by screening, assessed by relative risks compared with historical control groups from screening regions, national control groups from non-screening regions, and historical national control groups.
In total, 3279 invasive breast carcinomas and ductal carcinomas in situ occurred. The start of screening led to prevalence peaks in breast cancer incidence: relative risk 2.06 (95% confidence interval 1.64 to 2.59) for Copenhagen and 1.84 (1.46 to 2.32) for Funen. During subsequent screening rounds, relative risks were slightly above unity: 1.04 (0.85 to 1.27) for Copenhagen and 1.14 (0.98 to 1.32) for Funen. A compensatory dip was seen after the end of invitation to screening: relative risk 0.80 (0.65 to 0.98) for Copenhagen and 0.67 (0.55 to 0.81) for Funen during the first four years. The relative risk of breast cancer accumulated over the entire follow-up period was 1.06 (0.90 to 1.25) for Copenhagen and 1.01 (0.93 to 1.10) for Funen. Relative risks for participants corrected for selection bias were estimated to be 1.08 for Copenhagen and 1.02 for Funen; for participants followed for at least eight years after the end of screening, they were 1.05 and 1.01. A pooled estimate gave 1.040 (0.99 to 1.09) for all targeted women and 1.023 (0.97 to 1.08) for targeted women followed for at least eight years after the end of screening.
On the basis of combined data from the two screening programmes, this study indicated that overdiagnosis most likely amounted to 2.3% (95% confidence interval -3% to 8%) in targeted women. Among participants, it was most likely 1-5%. At least eight years after the end of screening were needed to compensate for the excess incidence during screening.

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Available from: Ilse Vejborg, Mar 11, 2014
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    • "None of the studies included in the previous reviews of colorectal cancer surveillance have provided any specific details of the harms (mortality or morbidity) resulting from investigating or treating recurrences [2,3]. However, a potential harm from any secondary prevention program is well recognised to be over-diagnosis and false positive tests [7,11]. "
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    ABSTRACT: The survival benefits of colon cancer surveillance programs are well delineated, but less is known about the magnitude of false positive testing. The objective of this study was to estimate the false positive rate and positive predictive value of testing as part of a surveillance program based on national guidelines, and to estimate the degree of testing and resource use needed to identify a curable recurrence. Analysis of clinically significant events leading to suspicion of cancer recurrence, false positive events, true cancer recurrences, time to confirmation of diagnosis, and resource use (radiology, blood samples, colonoscopies, consultations) among patients included in a randomised colon cancer surveillance trial. 110 patients surgically treated for colon cancer were followed according to national guidelines for 1884 surveillance months. 1105 tests (503 blood samples, 278 chest x-rays, 209 liver ultrasounds, 115 colonoscopies) and 1186 health care consultations were performed. Of the 48 events leading to suspicion of cancer recurrence, 34 (71%) represented false positives. Thirty-one (65%) were initiated by new symptoms, and 17 (35%) were initiated by test results. Fourteen patients had true cancer recurrence; 7 resections of recurrent disease were performed, 4 of which were successful R0 metastasis Resections. 276 tests and 296 healthcare consultations were needed per R0 resection; the cost per R0 surgery was [pound sign] 103207. There was a 29% probability (positive predictive value) of recurrent cancer when a diagnostic work-up was initiated based on surveillance testing or patient complaints. We observed a high false positive rate and low positive predictive value for significant clinical events suggestive of possible colorectal cancer relapse in the setting of a post-treatment surveillance program based on national guidelines. Providers and their patients should have an appreciation for the modest positive predictive value inherent in colorectal cancer surveillance programs in order to make informed choices, which maximize quality of life during survivorship. Better means of tailoring surveillance programs based on patient risk would likely lead to more effective and cost-effective post-treatment follow-up.Trial registration: identifier NCT00572143. Date of trial registration: 11th of December 2007.
    BMC Health Services Research 03/2014; 14(1):137. DOI:10.1186/1472-6963-14-137 · 1.71 Impact Factor
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    • "Estimates of overdiagnosis have included either only invasive cancers, or both invasive and ductal carcinoma in situ (DCIS) which are most often identified through mammography. Several recent cohort analyses were published from Norway [2], Denmark [21], and Italy [22] using a record linkage design with information on screening invitations or participations from program registries, and outcomes from cancer registries. The estimated overdiagnosis varied from almost zero to around ten percent when the years after the end of active screening were included. "
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    ABSTRACT: There is increasing ambiguity towards national mammographic screening programs due to varying publicized estimates of overdiagnosis, i.e., breast cancer that would not have been diagnosed in the women's lifetime outside screening. This analysis compares the cumulative incidence of breast cancer in screened and unscreened women in Norway from the start of the fully implemented Norwegian Breast Cancer Screening Program (NBCSP) in 2005. Subjects were 53 363 women in the Norwegian Women and Cancer (NOWAC) study, aged 52-79 years, with follow-up through 2010. Mammogram and breast cancer risk factor information were taken from the most recent questionnaire (2002-07) before the start of individual follow-up. The analysis differentiated screening into incidence (52-69 years) and post screening (70-79 years). Relative risks (RR) were estimated by Poisson regression. The analysis failed to detect a significantly increased cumulative incidence rate in screened versus other women 52-79 years. RR of breast cancer among women outside the NBCSP, the "control group", was non-significantly reduced by 7% (RR = 0[bullet operator]93 ; 95% confidence interval 0[bullet operator]79 to 1[bullet operator]10) compared to those in the program. The RR was attenuated when adjusted for risk factors; RRadj = 0[bullet operator]97 (0[bullet operator]82 to 1[bullet operator]15). The control group consisted of two subpopulations, those who only had a mammogram outside the program (RRadj =1[bullet operator]04 ; 0[bullet operator]86 to 1[bullet operator]26) and those who never had a mammogram (RRadj = 0[bullet operator]77 ; 0[bullet operator]59 to 1[bullet operator]01). These groups differed significantly with respect to risk factors for breast cancer, partly as a consequence of the prescription rules for hormone therapy which indicate a mammogram. In the fully implemented NBCSP, no significant difference was found in cumulative incidence rates of breast cancer between NOWAC women screened and not screened. Naive comparisons of screened and unscreened women may be affected by important differences in risk factors. The current challenge for the screening program is to improve the diagnostics used at prevalence screenings (ages 50-51).
    BMC Cancer 12/2013; 13(1):614. DOI:10.1186/1471-2407-13-614 · 3.36 Impact Factor
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    • "Alternatively, the life-time risk of overdiagnosis can be calculated by including all cancers, also all those detected after screening stopped. Most researchers add cancers detected in a 5–15 years period after screening has stopped, arguing that this is a sufficient adjustment for lead time (Smith et al, 2004; Seigneurin et al, 2011; Kalager et al, 2012; Njor et al, 2013). Here we discuss how clinical lead time can be estimated and how adjustment for clinical and model-based lead times gives fundamentally different estimates of overdiagnosis. "
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    ABSTRACT: Background: Published lead time estimates in breast cancer screening vary from 1 to 7 years and the percentages of overdiagnosis vary from 0 to 75%. The differences are usually explained as random variations. We study how much can be explained by using different definitions and methods. Methods: We estimated the clinically relevant lead time based on the observed incidence reduction after attending the last screening round in the Norwegian mammography screening programme. We compared this estimate with estimates based on models that do not take overdiagnosis into account (model-based lead times), for varying levels of overdiagnosis. Finally, we calculated overdiagnosis adjusted for clinical and model-based lead times and compared results. Results: Clinical lead time was about one year based on the reduction in incidence in women previously offered screening. When overdiagnosed tumours were included, the estimates increased to 4–9 years, depending on the age at which screening begins and the level of overdiagnosis. Including all breast cancers detected in women long after the end of the screening programme dilutes the level of overdiagnosis by a factor of 2–3. Conclusion: When overdiagnosis is not taken into account, lead time is substantially overestimated. Overdiagnosis adjusted for model-based lead time is a function tending to zero, with no simple interpretation. Furthermore, the estimates are not in general comparable, because they depend on both the duration of screening and duration of follow-up. In contrast, overdiagnosis adjusted for clinically relevant tumours is a point estimate (and interpreted as percentage), which we find is the most reasonable method.
    British Journal of Cancer 08/2013; 109(7). DOI:10.1038/bjc.2013.427 · 4.84 Impact Factor
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