Quantitative Interpretation of Age-Specific Mortality Reductions From the Swedish Breast Cancer-Screening Trials

Koning, Harry J. de; Boer, Rob; Warmerdam, Peter G.; Beemsterboer, Petra M. M.; Maas, P.J. van der

doi:10.1093/jnci/87.16.1217

Cited by 155 publications

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“…Estimates of mortality reduction from screening in women under 50 have so far come primarily from subgroup analyses of randomised controlled trials recruiting cohorts of women from ages 40 or 45 upwards; meta-analyses of these trials have estimated a reduction of 18% at an average of 12.7 years of follow-up in women aged 40 -49 at entry (Hendrick et al, 1997), but there remains debate as to how much of this effect is due to screening occurring after age 50 (de Koning et al, 1995). The results of these trials are summarised in Table 5, to allow comparison with the UK trial.…”

Section: Discussionmentioning

confidence: 99%

Randomised controlled trial of mammographic screening in women from age 40: predicted mortality based on surrogate outcome measures

et al. 2005

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A trial in the UK to study the effect on mortality from breast cancer of invitation for annual mammography from the age of 40 -41, has randomised a total of 160 921 women in the ratio 1 : 2 to the intervention and control arms. All breast cancers diagnosed in the two arms have been identified, and the histology reviewed. This paper presents the results of an interim analysis using surrogate outcome measures to compare predicted breast cancer mortality in the two arms based on 1287 cases diagnosed to 31.12.1999. Due to earlier diagnosis, there is currently an 8% excess of invasive breast cancers in the intervention arm. The ratio of predicted deaths at 10 years in the intervention arm relative to the control arm, adjusted for this excess diagnosis, ranges from 0.89 (95% confidence interval (CI) 0.78 -1.01) to 0.90 (95% CI 0.80 -1.01). Screening from age 40 may result in a lower reduction in breast cancer mortality than that observed in other trials including women below age 50. This analysis based on surrogate outcome measures suggests that a reduction in breast cancer mortality may be observed in this trial. However, a number of assumptions have been necessary and firm conclusions must await the analysis of observed mortality from breast cancer. At the time the NHS breast screening programme (NHSBSP) was introduced in 1988, evidence from the randomised controlled trials suggested that the benefit of screening was restricted to women aged 50 and over, and it was decided to include women aged 50 -64 in the invitation system. The current Age Trial was established to investigate the benefit of screening in younger women, specifically the effectiveness of inviting women annually between the ages of 40 and 47 -48.The primary outcome measure of the trial is mortality from breast cancer. However, detailed pathology information on all breast cancer cases in the trial is also being collected, in order to permit an earlier analysis of surrogate outcome measures to be performed. MATERIALS AND METHODSThe methodology of the trial has been described in detail elsewhere (Moss, 1999). Briefly, 160 921 women have been randomised in the ratio 1 : 2 to an intervention arm and to a control arm.Randomisation is individual, stratified by GP practice. Women in the intervention arm are invited annually for screening by mammography (by two views at first screen, and one view thereafter unless otherwise indicated.) Women in the control arm receive usual medical care. The original protocol to offer each woman seven annual screens was subsequently extended to include invitations up to the calendar year of each woman's 48th birthday. Ethics approval was obtained from London (formerly North Thames) MREC. Sample sizeThe trial was designed to randomise 195 000 women aged 40 -41 at entry, in order to have 80% power to detect a 20% reduction in breast cancer mortality at 10 years of follow-up in the intervention arm, at the 5% significance level, using a one-sided test. This was based on an estimated mortality of 3.3 per 1000 in the control arm i...

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Section: Discussionmentioning

confidence: 99%

Randomised controlled trial of mammographic screening in women from age 40: predicted mortality based on surrogate outcome measures

et al. 2005

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“…12 We predicted breast cancer mortality using stage-specific improvement in prognosis after screen detection based on the results of analyses of the 5 Swedish randomized controlled trials. 7 Although there has been much discussion about the methodologic quality of several of these trials, 2,19 the general consensus is that their findings are valid. 1,20 Improvement in prognosis after screen detection was based on breast cancer mortality reductions in women aged 50 -69 years.…”

Section: Discussionmentioning

confidence: 99%

“…The MISCAN breast cancer-screening model 6,7 was used to analyze the results of both study arms of the CNBSS-2. A detailed description of the model is given in the Appendix.…”

Section: Implementation Of Demographic Epidemiologic and Screening Cmentioning

confidence: 99%

“…We first used the improvement in prognosis after screen detection based on the results of analyses of the 5 Swedish mammography screening trials, which was estimated to be 1.000, 0.892, 0.814, 0.567 and 0.395, respectively, for cancers screendetected in stages DCIS, T1a, T1b, T1c and T2ϩ. 7 The effect of alternative assumptions for the improvement in prognosis after screen detection on expected mortality results (of model C) was also explored. We calculated 95% CIs for breast cancer mortality using the Poisson distribution.…”

Section: Breast Cancer Mortalitymentioning

confidence: 99%

“…MISCAN is a microsimulation program, which has been successfully applied in the evaluation of different cancer-screening programs. [5][6][7] The main purpose of the model evaluation is to show what can be learned about breast cancer screening for women aged 50 and above and about the natural history of the disease from the CNBSS-2 in relation to what we know from other breast cancerscreening trials. The evaluation addresses 2 specific questions: (i) Can any explanations, resulting from the model evaluation, be given for the observed equal breast cancer mortality in both study arms of the CNBSS-2?…”

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Mammography benefit in the Canadian National Breast Screening Study‐2: A model evaluation

Rijnsburger

Oortmarssen

Boer

et al. 2004

Intl Journal of Cancer

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The CNBSS-2 among women aged 50 -59 did not show any significant difference in breast cancer mortality between a control arm screened annually by CBE and a study arm screened by CBE and mammography. Because of this design, the benefit of screening compared to no screening could not be evaluated. We therefore conducted a modeling effort to estimate the benefit of mammography or CBE compared to no screening. We incorporated demographic, epidemiologic and screening characteristics of the CNBSS-2 in MISCAN. Stage-specific sensitivities of CBE, with and without mammography, and breast cancer incidence rate in the trial were estimated by comparing observed trial data with model predictions. We predicted the number of breast cancer deaths for both study arms of the CNBSS-2 and in the absence of screening, assuming improvement in prognosis by early detection. We estimated a 24 -29% higher breast cancer incidence rate in the CNBSS-2 than the average Canadian rate. Key words: breast cancer; screening; mortality; mammography; clinical breast examination; Canadian National Breast Screening Study-2Several randomized controlled trials have assessed the efficacy of mammography screening at reducing breast cancer mortality. An updated overview of 4 Swedish randomized trials showed breast cancer mortality reductions in invited women of 16% (50 -59 years) and 33% (60 -69 years). 1 However, in a Cochrane review, the authors found smaller breast cancer mortality reductions in 2 so-called medium-quality trials. 2 The Malmö trial and the CNBSS-2 showed 20% (Ն55 years) and 3% (50 -59 years) breast cancer mortality reductions after 7 years of follow-up.The CNBSS-2, however, was designed to evaluate the efficacy of annual mammography over and above annual CBE. The 7-and 13-year follow-up results of this randomized trial did not show a significant difference in mortality from breast cancer between the 2 groups, even though high detection rates were found. 3,4 Because the control arm was screened, no estimations of mammography benefit compared to no screening could be made, as is available from other mammography trials, nor any estimate of the benefit of CBE screening.Here, we provide a quantitative interpretation of the CNBSS-2 results, using a MISCAN model evaluation of the trial. MISCAN is a microsimulation program, which has been successfully applied in the evaluation of different cancer-screening programs. [5][6][7] The main purpose of the model evaluation is to show what can be learned about breast cancer screening for women aged 50 and above and about the natural history of the disease from the CNBSS-2 in relation to what we know from other breast cancerscreening trials. The evaluation addresses 2 specific questions: (i) Can any explanations, resulting from the model evaluation, be given for the observed equal breast cancer mortality in both study arms of the CNBSS-2? (ii) What percentage of breast cancer mortality reduction by mammography screening compared to no screening can we estimate for the CNBSS-2? MATERIAL AND METHODS CNB...

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The New Era in Breast Cancer

Cady

Stone²,

Schuler³

et al. 1996

Arch Surg

335

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Within the next decade, the proportion of all breast cancers that are ductal carcinoma in situ will approach 33%, and invasive cancers will approach 1 cm in median maximum diameter. Therapy simplification will be logical because of very small size, low risk of recurrence after breast conservation, and excellent prognosis, and might include increased breast conservation, avoidance of axillary nodal dissection, and omission of radiation therapy to conserve breasts. Adjuvant therapy will be based on the prognostic features of the primary cancer and findings from careful histologic examination of the sentinel lymph nodes.

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Quantitative Interpretation of Age-Specific Mortality Reductions From the Swedish Breast Cancer-Screening Trials

Abstract: Detailed screening data for the 40- to 49-year age group of all Swedish trials should be analyzed to specifically estimate the natural history and performance of screening in this age group.

Cited by 155 publications

References 0 publications

Randomised controlled trial of mammographic screening in women from age 40: predicted mortality based on surrogate outcome measures

Randomised controlled trial of mammographic screening in women from age 40: predicted mortality based on surrogate outcome measures

Mammography benefit in the Canadian National Breast Screening Study‐2: A model evaluation

The New Era in Breast Cancer

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