| 1. |
- Carninci, P, et al.
(författare)
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The transcriptional landscape of the mammalian genome
- 2005
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5740, s. 1559-1563
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Tidskriftsartikel (refereegranskat)abstract
- This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5′ and 3′ boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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| 2. |
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| 4. |
- Larsson, LG, et al.
(författare)
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The Swedish randomised mammography screening trials: analysis of their effect on the breast cancer related excess mortality
- 1996
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Ingår i: Journal of medical screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 3:3, s. 129-32
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Tidskriftsartikel (refereegranskat)abstract
- –To apply an indirect method for estimation of the breast cancer related excess mortality in the Swedish randomised mammography screening trials.Setting–Randomised trials on mammography screening have, in Sweden, been performed in the counties of Kopparberg (W) and Östergötland (E), the so called WE study, and in the three largest cities in Sweden, Stockholm (southern part), Gothenburg, and Malmö. An overview of the trials was presented in the Lancet in 1993 and included 156 911 women in the invited group and 125 866 in the control group.Methods–The excess mortality in the breast cancer subgroups was estimated by indirect standardisation using official national cause of death statistics according to Statistics Sweden as a reference. Results—The estimated reduction of the breast cancer related mortality was 24% for the whole group (40–74 years at randomisation). The corresponding figures for the age groups 40–49, 50–59, and 60–69 years were 6%, 28%, and 34% respectively.Conclusion–The results are very similar to those presented earlier based on the traditional comparison of the breast cancer mortality in the invited and in the control group. This analysis further strengthens previous reports on a beneficial effect of mammography screening, which is especially pronounced in the age group 50–69.
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| 5. |
- Duffy, S, et al.
(författare)
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Estimates of overdiagnosis from two trials of mammographic screening for breast cancer
- 2005
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 7:6, s. 258-265
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Tidskriftsartikel (refereegranskat)abstract
- Randomised controlled trials have shown that the policy of mammographic screening confers a substantial and significant reduction in breast cancer mortality. This has often been accompanied, however, by an increase in breast cancer incidence, particularly during the early years of a screening programme, which has led to concerns about overdiagnosis, that is to say, the diagnosis of disease that, if left undetected and therefore untreated, would not become symptomatic. We used incidence data from two randomised controlled trials of mammographic screening, the Swedish Two-county Trial and the Gothenburg Trial, to establish the timing and magnitude of any excess incidence of invasive disease and ductal carcinoma in situ (DCIS) in the study groups, to ascertain whether the excess incidence of DCIS reported early in a screening trial is balanced by a later deficit in invasive disease and provide explicit estimates of the rate of 'real' and non-progressive 'overdiagnosed' tumours from the study groups of the trials. We used a multistate model for overdiagnosis and used Markov Chain Monte Carlo methods to estimate the parameters. After taking into account the effect of lead time, we estimated that less than 5% of cases diagnosed at prevalence screen and less than 1 % of cases diagnosed at incidence screens are being overdiagnosed. Overall, we estimate overdiagnosis to be around 1 % of all cases diagnosed in screened populations. These estimates are, however, subject to considerable uncertainty. Our results suggest that overdiagnosis in mammography screening is a minor phenomenon, but further studies with very large numbers are required for more precise estimation. © 2005 BioMed Central Ltd.
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| 7. |
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| 10. |
- Nystrom, L, et al.
(författare)
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An overview of the Swedish randomised mammography trials: total mortality pattern and the representivity of the study cohorts
- 1996
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Ingår i: Journal of medical screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 3:2, s. 85-7
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Tidskriftsartikel (refereegranskat)abstract
- –To analyse the cause of death pattern in the cohorts of women included in the Swedish randomised mammography screening trials by comparing the groups of invited and control women both with each other and with the general population of Swedish women. Setting –Since 1977 four randomised trials of mammography screening have been performed in Sweden: Malmö, Kopparberg and ÖOstergötland (the two county trial), Stockholm, and Gothenburg. Design –Overview of four randomised mammography screening trials. Results –The total numbers of deaths in the invited and control groups respectively were 15 695 and 11 887 corresponding to a relative risk (RR) of 1.00. There were no significant differences between the invited and control groups for cause-specific mortality, except for breast cancer. When the total mortality in the invited and the control groups was compared with that for Swedish women in general the standardised mortality ratio was close to 100. Conclusions –The cause of death pattern in the invited group was, except for breast cancer, very similar to that in the control group, showing that the groups were comparable. Similarly, the total mortality including breast cancer mortality in the control group was almost identical to that in Swedish women in general. The same was true, with the exception of breast cancer, for the invited group. These observations confirm that the trial cohorts are representative of Swedish women and indicate that the quantitative results from these trials may safely be generalised to the Swedish population.
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| 12. |
- Brem, Rachel F., et al.
(författare)
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Assessing Improvement in Detection of Breast Cancer with Three-dimensional Automated Breast US in Women with Dense Breast Tissue : The Somoinsight Study
- 2015
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Ingår i: Radiology. - : Radiological Society of North America (RSNA). - 0033-8419 .- 1527-1315. ; 274:3, s. 663-673
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To determine improvement in breast cancer detection by using supplemental three-dimensional (3D) automated breast (AB) ultrasonography (US) with screening mammography versus screening mammography alone in asymptomatic women with dense breasts. Materials and Methods: Institutional review board approval and written informed consent were obtained for this HIPAA-compliant study. The SomoInsight Study was an observational, multicenter study conducted between 2009 and 2011. A total of 15 318 women (mean age, 53.3 years +/- 10 [standard deviation]; range, 2594 years) presenting for screening mammography alone with heterogeneously (50%75%) or extremely (>75%) dense breasts were included, regardless of further risk characterization, and were followed up for 1 year. Participants underwent screening mammography alone followed by an AB US examination; results were interpreted sequentially. McNemar test was used to assess differences in cancer detection. Results: Breast cancer was diagnosed at screening in 112 women: 82 with screening mammography and an additional 30 with AB US. Addition of AB US to screening mammography yielded an additional 1.9 detected cancers per 1000 women screened (95% confidence interval [CI]: 1.2, 2.7; P < .001). Of cancers detected with screening mammography, 62.2% (51 of 82) were invasive versus 93.3% (28 of 30) of additional cancers detected with AB US (P = .001). Of the 82 cancers detected with either screening mammography alone or the combined read, 17 were detected with screening mammography alone. Of these, 64.7% (11 of 17) were ductal carcinoma in situ versus 6.7% (two of 30) of cancers detected with AB US alone. Sensitivity for the combined read increased by 26.7% (95% CI: 18.3%, 35.1%); the increase in the recall rate per 1000 women screened was 284.9 (95% CI: 278.0, 292.2; P < .001). Conclusion: Addition of AB US to screening mammography in a generalizable cohort of women with dense breasts increased the cancer detection yield of clinically important cancers, but it also increased the number of false-positive results. (C)RNSA, 2014.
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| 16. |
- Duffy, SW, et al.
(författare)
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Correcting for non-compliance bias in case-control studies to evaluate cancer screening programmes
- 2002
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Ingår i: The Journal of the Royal Statistical Society, Series C. - 0035-9254 .- 1467-9876. ; 51, s. 235-243
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Tidskriftsartikel (refereegranskat)abstract
- In the evaluation of uncontrolled service screening programmes for cancer, the case-control design is sometimes used, in which people who die from the disease in question are compared with live controls with respect to screening histories, Such a design tends to yield estimates of relative mortality in voluntary participants compared with non-participants. This may bias results, since compliers and non-compliers may differ a priori in ways which are not related to screening but which nevertheless affect the risk of death from the disease. We present a simple method, employing external data from previously published randomized controlled trials of screening, of correction for this bias. We illustrate it by using data from a case-control study performed within the invited arm of the Malmo mammographic screening trial, a prospective study from the service screening programme in two counties in Sweden, and a matched case-control study of mammographic screening in Florence, Italy.
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| 18. |
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| 19. |
- Duffy, SW, et al.
(författare)
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The relative contributions of screen-detected in situ and invasive breast carcinomas in reducing mortality from the disease
- 2003
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 39:12, s. 1755-1760
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to quantify the benefits of detecting ductal carcinoma in situ (DCIS) and of downwards stage-shifting within invasive tumours in mammographic screening. Using data from the Swedish Two-County Trial of breast cancer screening, we examined the 20-year death rates from invasive tumours of stage II or worse, invasive tumours of stage I and DCIS. We then used these rates and their respective incidences in invited (active study population, ASP) and control (passive study population, PSP) arms of the trial, to estimate the numbers of deaths avoided by downward stage-shifting the larger stage II or worse tumours to stage I and the stage I cancers to DCIS. We also studied the association between the mortality reduction achieved and the proportion of DCIS cases detected in the randomised trials of breast cancer screening. In the Swedish Two County Trial, 141 breast cancer deaths were avoided in the ASP compared with the PSP at approximately 20 years of follow-up. Of these, 65% (91/141) were avoided as a result of stage-shifting from invasive stage II or worse to invasive stage I, and 5% (7/141) as a result of stage-shifting from invasive stage I to DCIS. If we assumed that 10% of stage II or worse tumours avoided were shifted not to stage I, but to DCIS, the estimated number of deaths prevented by shifting from invasive disease to in situ was 17, which is 12% of all deaths prevented. When the results of all the randomised trials of breast cancer screening were reviewed, there was no clear association between the percentage of DCIS cases diagnosed and the observed mortality reduction. We conclude that compared with downward stage-shifting of invasive tumours, detection of DCIS plays a small part in saving lives from breast cancer. Treatment decisions in DCIS, as in invasive carcinoma, should take full account of histopathological, clinical and radiological attributes of the tumour. ⌐ 2003 Elsevier Ltd. All rights reserved.
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| 20. |
- Duffy, S. W., et al.
(författare)
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Overdiagnosis and overtreatment of breast cancer: estimates of overdiagnosis from two trials of mammographic screening for breast cancer
- 2005
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Ingår i: Breast Cancer Res. - 1465-542X. ; 7:6, s. 258-65
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Tidskriftsartikel (refereegranskat)abstract
- Randomised controlled trials have shown that the policy of mammographic screening confers a substantial and significant reduction in breast cancer mortality. This has often been accompanied, however, by an increase in breast cancer incidence, particularly during the early years of a screening programme, which has led to concerns about overdiagnosis, that is to say, the diagnosis of disease that, if left undetected and therefore untreated, would not become symptomatic. We used incidence data from two randomised controlled trials of mammographic screening, the Swedish Two-county Trial and the Gothenburg Trial, to establish the timing and magnitude of any excess incidence of invasive disease and ductal carcinoma in situ (DCIS) in the study groups, to ascertain whether the excess incidence of DCIS reported early in a screening trial is balanced by a later deficit in invasive disease and provide explicit estimates of the rate of 'real' and non-progressive 'overdiagnosed' tumours from the study groups of the trials. We used a multistate model for overdiagnosis and used Markov Chain Monte Carlo methods to estimate the parameters. After taking into account the effect of lead time, we estimated that less than 5% of cases diagnosed at prevalence screen and less than 1% of cases diagnosed at incidence screens are being overdiagnosed. Overall, we estimate overdiagnosis to be around 1% of all cases diagnosed in screened populations. These estimates are, however, subject to considerable uncertainty. Our results suggest that overdiagnosis in mammography screening is a minor phenomenon, but further studies with very large numbers are required for more precise estimation.
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| 21. |
- Duffy, S.W., et al.
(författare)
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The Swedish two-county trial of mammographic screening : Cluster randomisation and end point evaluation
- 2003
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 14:8, s. 1196-1198
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Swedish Two-County Trial has been criticised on the grounds of the cluster randomisation and alleged bias in classification of cause of death. Patients and methods: In the Two-County Trial, 77080 women were randomised to regular invitation to screening (active study population, ASP) and 55985 to no invitation (passive study population, PSP), in 45 geographical clusters. After ~7 years, the PSP was invited to screening and the trial closed. We analysed data using hierarchical statistical models to take account of cluster randomisation, and performed a conservative analysis assuming a systematic difference between ASP and PSP in baseline breast cancer mortality in one of the counties. We also analysed deaths from causes other than breast cancer and from all causes among breast cancer cases diagnosed in the ASP and PSP. Results: Taking account of the cluster randomisation there was a significant 30% reduction in breast cancer mortality in the ASP. Conservatively, assuming a systematic difference between ASP and PSP clusters in baseline breast cancer mortality, there was a significant 27% reduction in mortality in the ASP. Ignoring classification of cause of death, there was a significant 13% reduction in all-cause mortality in breast cancer cases in the ASP. Conclusions: Breast cancer mortality is a valid end point and mammographic screening does indeed reduce mortality from breast cancer. The criticisms of the Swedish Two-County Trial are unfounded.
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| 22. |
- Duffy, S.W., et al.
(författare)
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Tumor size and breast cancer detection : What might be the effect of a less sensitive screening tool than mammography?
- 2006
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Ingår i: The Breast Journal. - 1075-122X .- 1524-4741. ; 12:SUPPL. 1
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Tidskriftsartikel (refereegranskat)abstract
- In some limited-resource areas, a state-of-the-art mammography program is not affordable. In such circumstances, one might consider a less resource-intensive, but also less sensitive screening tool such as clinical breast examination (CBE). We used data from the Swedish Two-County Trial to estimate the shift in tumor size resulting from invitation to mammographic screening. By postulating a lesser benefit of a less sensitive screening tool (CBE), particularly in terms of detecting very small tumors, we predicted its likely effect on tumor size distribution. In addition, using the observed association between tumor size and nodal status, and between tumor size and fatality, we predicted the likely benefit in terms of reductions in node-positive disease and in breast cancer mortality. An invitation to mammographic screening was associated with a 27% reduction in the number of node-positive tumors and a 31% reduction in the number of breast cancer deaths. We estimate that in the trial population, screening with CBE alone would have led to an 11% reduction in node-positive tumors and an 11% reduction in breast cancer deaths (approximately 42 deaths prevented per 1000 cases). Assuming instead a tumor size distribution typical of a limited-resource setting (70% of tumors are 30 mm at presentation), we estimate that screening with CBE alone would lead to a 13% reduction in node-positive tumors and a 12% reduction in breast cancer deaths (approximately 72 deaths prevented per 1000 cases). Thus, although the relative benefit of CBE is only slightly greater in the limited-resource setting, the absolute reduction in deaths per case is about 70% higher. Our findings suggest that a less sensitive tool might be expected to confer a breast cancer mortality reduction about half of that observed with mammography. © 2006 The Fred Hutchinson Cancer Research Center.
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