Breast cancer mortality and overdiagnosis after implementation of population-based screening in Denmark

Abstract

Introduction Service breast cancer screening is difficult to evaluate because there is no unscreened control group. Due to a natural experiment, where 20% of women were offered screening in two regions up to 17 years before other women, Denmark is in a unique position. We utilized this opportunity to assess outcome of service screening. Materials and methods Screening was offered in Copenhagen from 1991 and Funen from 1993 to women aged 50-69 years. We used difference-indifferences methodology with a study group offered screening; a historical control group; a regional control group; and a regional-historical control group, comparing breast cancer mortality and incidence, including ductal carcinoma in situ, between study and historical control group adjusted for changes in other regions, and calculating ratios of rate ratios (RRR) with 95% confidence intervals (CI). Data came from Central Population Register; mammography screening databases; Cause of Death Register; and Danish Cancer Register. Results For breast cancer mortality, the study group accumulated 1,551,465 person-years and 911 deaths. Long-term breast cancer mortality in Copenhagen was 20% below expected in absence of screening; RRR 0.80 (95% CI 0.71-0.90), and in Funen 22% below; RRR 0.78 (95% CI 0.68-0.89). Combined, cumulative breast cancer incidence in women followed 8+ years post-screening was 2.3% above expected in absence of screening; RRR 1.023 (95% CI 0.97-1.08). Discussion Benefit-to-harm ratio of the two Danish screening programs was 2.6 saved breast cancer deaths per overdiagnosed case. Screening can affect only breast cancers diagnosed in screening age. Due to high breast cancer incidence after age 70, only one-third of breast cancer deaths after age 50 could potentially be affected by screening. Increasing upper age limit could be considered, but might affect benefit-to-harm ratio negatively.

Irregular screening participation increases advanced stage breast cancer at diagnosis: A population-based study

“…Hence the relationship between participation regularity and the risk of advanced stage breast cancer at diagnosis can be biased. To evaluate the effect of overdiagnosis on the association between screening regularity and the risk of advanced stage breast cancer at diagnosis in our estimation, a sensitive analysis assumes a 10% overdiagnosis rate derived from the Dutch population [22,23] was performed, since the level of overdiagnosis in Flanders breast cancer screening programme has not been reported in literature, we applied the data from the Dutch population which is geographically nearby the Flanders region [24][25][26][27][28][29][30][31]. In this sensitivity analysis, a random 10% of early stage screen-detected breast cancers were excluded and the modeling was done in the rest of the cases, since by definition, overdiagnosis is due to the detection of breast cancer that are not progressive at early stage by screening mammograms.…”

Benefits and harms of breast cancer screening: Cohort study of breast cancer mortality and overdiagnosis

“…Another recent cohort study from Sweden of attendees and non‐attendees used a Markov model to estimate overdiagnosis and concluded it was minimal 14 . A cohort study from Denmark of invitation reported almost no overdiagnosis 11,15 …”

“…14 A cohort study from Denmark of invitation reported almost no overdiagnosis. 11,15 For an Australian case-control study included in the IARC handbook, 41 we calculated the odds ratio for all breast cancer in relation to ever having attended BreastScreen of 1.15 (CI 1.09-1.22), giving an attributable fraction of 13.4%. The study did not exclude women who previously had mammography or other breastrelated diagnostic procedures through Medicare.…”

“…10 In contrast, cohort studies can be used to estimate risk, but of the 40 analyses of overdiagnosis described in the IARC handbook, only 10 were cohort studies. 1 Several cohort studies and one case-control study were published after the IARC handbook [11][12][13][14][15][16] ; one by Lund et al 13 updated an earlier analysis. 17 Quantifying the balance of benefits and harms of screening is important for helping women to make informed choices about whether to participate in screening, but estimates differ.…”

Evaluating cancer screening programs using survival analysis

“…The literature in this field is rich with various study designs (e.g., randomized clinical trials, case‐control studies, the difference‐in‐difference designs, etc. ; Adami et al., 2020; Lynge et al., 2020; Maroni et al., 2020), outcome measures (e.g., incidence, mortality, number needed to screen, stage shift, survival probability, etc. ; Duffy & Smith, 2020; Owens et al., 2022; Rembold, 1998), and comparisons used to evaluate CSPs.…”