Objectives To evaluate the effect on breast cancer mortality during the first 10 years of the mammography service screening programme that was introduced in Copenhagen in 1991. Design Cohort study. Setting The mammography service screening programme in Copenhagen, Denmark. Participants All women ever invited to mammography screening in the first 10 years of the programme. Historical, national, and historical national control groups were used. Main outcome measures The main outcome measure was breast cancer mortality. We compared breast cancer mortality in the study group with rates in the control groups, adjusting for age, time period, and region. Results Breast cancer mortality in the screening period was reduced by 25% (relative risk 0.75, 95% confidence interval 0.63 to 0.89) compared with what we would expect in the absence of screening. For women actually participating in screening, breast cancer mortality was reduced by 37%. Conclusions In the Copenhagen programme, breast cancer mortality was reduced without severe negative side effects for the participants.
Objective To use data from two longstanding, population based screening programmes to study overdiagnosis in screening mammography.Design Population based cohort study.Setting Copenhagen municipality (from 1991) and Funen County (from 1993), Denmark.Participants 57 763 women targeted by organised screening, aged 56-69 when the screening programmes started, and followed up to 2009. Main outcome measuresOverdiagnosis 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. ResultsIn 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. ConclusionsOn 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.
Fifty-four patients with advanced breast cancer who had failed prior non-anthracycline combination chemotherapy were randomized to treatment with either epirubicin 85 mg/m2 or doxorubicin 60 mg/m2 intravenously every three weeks. Of 52 evaluable patients, 25% (six of 24) treated with epirubicin, and 25% (seven of 28) treated with doxorubicin experienced major therapeutic responses. The median duration of response to epirubicin was 11.9 months compared to 7.1 months with doxorubicin. Cardiotoxicity was monitored by serial multigated radionuclide cineangiocardiography performed at rest and after exercise. Laboratory evidence of cardiotoxicity was defined as a decrease in resting left ventricular ejection fraction of greater than 10% from the baseline value, or a decrease of 5% or greater with exercise compared with the resting study performed on the same day. Fifteen patients treated with epirubicin and 18 patients treated with doxorubicin had at least two determinations of left ventricular ejection fraction and were evaluable for laboratory cardiotoxicity. Using methods of survival analysis, the median doses to the development of laboratory cardiotoxicity were estimated to be 935 mg/m2 of epirubicin and 468 mg/m2 of doxorubicin. Four patients treated with epirubicin and five treated with doxorubicin developed symptomatic congestive heart failure. The median cumulative dose at which congestive heart failure occurred was 1,134 mg/m2 of epirubicin compared with 492 mg/m2 of doxorubicin. Fewer episodes of nausea and vomiting were observed in patients receiving epirubicin. Epirubicin is a new anthracycline with reduced cardiac toxicity, but preserved efficacy in the treatment of patients with advanced breast cancer.
Objectives The objectives of this study was to provide a simple estimate of the cumulative risk of a false-positive test for women participating in mammography screening. To test the method, we used data from two well-established, organized mammography screening programmes offering biennial screening to women aged 50-69 years in Copenhagen and Fyn, Denmark. Methods We defined the outcome from a screen as being either a false-positive test or not a falsepositive test. We then tested whether the outcomes from subsequent screens were independent, and afterwards estimated the risk over 10 screens of a false-positive test, i.e. the risk of getting at least one false-positive test for a woman participating in all 10 screens typically offered in Europe. Results The outcomes of subsequent screens were found to be independent. After completion of screening rounds 3-5, the risk of a false-positive test over 10 screens was predicted to be 15.8-21.5% for a woman participating in the programme in Copenhagen, and 8.1-9.6% for a woman participating in the programme in Fyn. Conclusions Our study showed that a relatively robust prediction of the risk of a false-positive test over 10 screens can be calculated in a simple way relatively early after the start of a mammography screening programme.
Objectives: When estimating the decline in breast cancer mortality attributable to screening, the challenge is to provide valid comparison groups and to distinguish the screening effect from other effects. In Funen, Denmark, multidisciplinary breast cancer management teams started before screening was introduced; both activities came later in the rest of Denmark. Because Denmark had national protocols for breast cancer treatment, but hardly any opportunistic screening, Funen formed a ''natural experiment'', providing valid comparison groups and enabling the separation of the effect of screening from other factors. Methods: Using Poisson regression we compared the observed breast cancer mortality rate in Funen after implementation of screening with the expected rate without screening. The latter was estimated from breast cancer mortality in the rest of Denmark controlled for historical differences between Funen/rest of Denmark. As multidisciplinary teams were introduced gradually in the rest of Denmark from 1994, the screening effect was slightly underestimated. Results: Over 14 years, women targeted by screening in Funen experienced a 22% (95% confidence interval 11%-32%) reduction in breast cancer mortality associated with screening (a reduction in breast cancer mortality rate from 61 to 47 per 100,000). The estimated reduction for participants corrected for selection bias was 28% (13%-41%). Excluding deaths in breast cancer cases diagnosed after end of screening, these numbers became 26% and 31%, respectively. Conclusions: There is additional benefit in reducing breast cancer mortality from the early detection of breast cancer through mammographic screening over and above the benefits arising from improvements in treatment alone.
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