Prue C Allgood

Absolute numbers of lives saved and overdiagnosis in breast cancer screening, from a randomized trial and from the Breast Screening Programme in England

Objectives To estimate the absolute numbers of breast cancer deaths prevented and the absolute numbers of tumours overdiagnosed in mammographic screening for breast cancer at ages 50–69 years. Setting The Swedish Two-County randomized trial of mammographic screening for breast cancer, and the UK Breast Screening Programme in England, ages 50–69 years. Methods We estimated the absolute numbers of deaths avoided and additional cases diagnosed in the study group (active study population) of the Swedish Two-County Trial, by comparison with the control group (passive study population). We estimated the same quantities for the mortality and incidence rates in England (1974–2004 and 1974–2003, respectively). We used Poisson regression for statistical inference. Results A substantial and significant reduction in breast cancer mortality was associated with screening in both the Two-County Trial (P < 0.001) and the screening programme in England (P < 0.001). The absolute benefits were estimated as 8.8 and 5.7 breast cancer deaths prevented per 1000 women screened for 20 years starting at age 50 from the Two-County Trial and screening programme in England, respectively. The corresponding estimated numbers of cases overdiagnosed per 1000 women screened for 20 years were, respectively, 4.3 and 2.3 per 1000. Conclusions The benefit of mammographic screening in terms of lives saved is greater in absolute terms than the harm in terms of overdiagnosis. Between 2 and 2.5 lives are saved for every overdiagnosed case.

Correcting for Lead Time and Length Bias in Estimating the Effect of Screen Detection on Cancer Survival

Determination of survival time among persons with screen-detected cancer is subject to lead time and length biases. The authors propose a simple correction for lead time, assuming an exponential distribution of the preclinical screen-detectable period. Assuming two latent categories of tumors, one of which is more prone to screen detection and correspondingly less prone to death from the cancer in question, the authors have developed a strategy of sensitivity analysis for various magnitudes of length bias. Here they demonstrate these methods using a series of 25,962 breast cancer cases (1988-2004) from the West Midlands, United Kingdom.

Explaining the difference in prognosis between screen-detected and symptomatic breast cancers

Background:We analysed 10-year survival data in 19 411 women aged 50–64 years diagnosed with invasive breast cancer in the West Midlands region of the United Kingdom. The aim was to estimate the survival advantage seen in cases that were screen detected compared with those diagnosed symptomatically and attribute this to shifts in prognostic variables or survival differences specific to prognostic categories.Methods:We studied tumour size, histological grade and the Nottingham Prognostic Index in very narrow categories and investigated the distribution of these prognostic factors within screen-detected and symptomatic tumours. We also adjusted for lead time bias.Results:The unadjusted 10-year breast cancer survival in screen-detected cases was 85.5% and in symptomatic cases 62.8%; after adjustment for lead time bias, survival in the screen-detected cases was 79.3%. Within narrow categories of prognostic variables, survival differences were small, indicating that the majority of the survival advantage of screen detection is due to differences in the distributions of size and node status.Conclusion:Our results suggested that a combination of lead time with size and node status in 10 categories explained almost all (97%) of the survival advantage. Only a small proportion remained to be explained by biological differences, manifested as length bias or overdiagnosis.

Prognosis and pathology of screen-detected carcinomas: how different are they?

It has been observed that screen‐detected breast cancers have a better prognosis than symptomatic tumors, even after taking pathological tumor attributes into account. This has led to the hypothesis that screen‐detected tumors are substantially biologically different from symptomatic cancers.

Population estimates of survival in women with screen-detected and symptomatic breast cancer taking account of lead time and length bias.

Background Evidence of the impact of breast screening is limited by biases inherent in non-randomised studies and often by lack of complete population data. We address this by estimating the effect of screen detection on cause-specific fatality in breast cancer, corrected for all potential biases, using population cancer registry data. Methods Subjects (N = 26,766) comprised all breast cancers notified to the West Midlands Cancer Intelligence Unit and diagnosed in women aged 50–74, from 1988 to 2004. These included 10,100 screen-detected and 15,862 symptomatic breast cancers (6,009 women with interval cancers and 9,853 who had not attended screening). Our endpoint was survival to death from breast cancer. We estimated the relative risk (RR) of 10-year cause-specific fatality (screen-detected compared to symptomatic cancers) correcting for lead time bias and performing sensitivity analyses for length bias. To exclude self-selection bias, survival analyses were also performed with interval cancers as the comparator symptomatic women. Findings Uncorrected RR associated with screen-detection was 0.34 (95% CI 0.31–0.37). Correcting for lead time, RR was 0.49 (95% CI 0.45–0.53); length bias analyses gave a range of RR corrected for both phenomena of 0.49–0.59, with a median of 0.51. Self-selection bias-corrected estimates yielded a median RR of 0.68. Interpretation After adjusting for various potential biases, women with screen-detected breast cancer have a substantial survival advantage over those with symptomatic breast cancer.

Translation of research results to simple estimates of the likely effect of a lung cancer screening programme in the United Kingdom

Background:There is considerable interest in the possibility of provision of lung cancer screening services in many developed countries. There is, however, no consensus on the target population or optimal screening regimen.Methods:In this paper, we demonstrate the use of published results on lung cancer screening and natural history parameters to estimate the likely effects of annual and biennial screening programmes in different risk populations, in terms of deaths prevented and of human costs, including screening episodes, further investigation rates and overdiagnosis.Results:Annual screening with the UK Lung Screening Study eligibility criteria was estimated to result in 956 lung cancer deaths prevented and 457 overdiagnosed cancers from 330 000 screening episodes. Biennial screening would result in 802 lung cancer deaths prevented and 383 overdiagnosed cancers for 180 000 screening episodes.Interpretation/conclusion:The predictions suggest that the intervention effect could justify the human costs. The evidence base for low-dose CT screening for lung cancer pertains almost entirely to annual screening. The benefit of biennial screening is subject to additional uncertainty but the issue merits further empirical research.

The impact of digital mammography on screening a young cohort of women for breast cancer in an urban specialist breast unit

ObjectiveTo compare the diagnostic performance of full-field digital mammography (FFDM) with screen-film mammography (SFM) in a corporate screening programme including younger women.MethodsData were available on 14,946 screening episodes, 5010 FFDM and 9936 SFM. Formal analysis was by logistic regression, adjusting for age and calendar year. FFDM is compared with SFM with reference to cancer detection rates, cancers presenting as clustering microcalcifications, recall rates and PPV of recall.ResultsOverall detection rates were 6.4 cancers per thousand screens for FFDM and 2.8 per thousand for SFM (p < 0.001). In women aged 50+ cancer detection was significantly higher for FFDM at 8.6 per thousand vs. 4.0 per thousand, (p = 0.002). In women <50, cancer detection was also significantly higher for FFDM at 4.3 per thousand vs. 1.4 per thousand, (p = 0.02). Cancers detected as clustering microcalcifications increased from 0.4 per thousand with SFM to 2.0 per thousand with FFDM. Rates of assessment recall were higher for FFDM (7.3% vs. 5.0%, p < 0.001). FFDM provided a higher PPV for assessment recall, (32 cancers/364 recalls, 8.8%) than SFM, (28 cancers/493 recalls, 5.7%).ConclusionsCancer detection rates were significantly higher for FFDM than for SFM, especially for women <50, and cancers detected as clustering microcalcifications.

Mammographic breast density by area of residence: possible evidence of higher density in urban areas.

ABSTRACT Objectives: A comparison of mammographic breast densities of women living in London with those of women living in rural and suburban areas. Design and methods: Using the standard four American College of Radiology Breast Imaging Reporting and Data System (BIRADS) categories of mammographic density, 318 mammograms of women from London and 654 mammograms of women from outside the capital aged 27–87 years who had received mammography at the Princess Grace Hospital, London, were assessed for density. The association between having any dense tissue and area of residence was assessed using both ordered and standard logistic regression, giving odds ratio estimates of relative risk of dense tissue adjusting for age. Results: Adjusting for age, London residents had significantly higher levels of density (OR = 1.32, 95% CI 1.04–1.70, p = 0.02). The major difference occurred in the age group 45–54 years and was most strongly manifested as a higher rate in London for density of 25% or more (BIRADS categories 2–4) as compared to almost entirely fatty (BIRADS 1) (OR = 2.22, 95% CI 1.05–4.68, p = 0.035). Conclusion: The higher density is likely to be due to a different prevalence of risk factors in the London population. This study cannot ascertain the reason for the higher density in this urban population, but the result is a cause for concern given that screening uptake is lower in London. Increased attention to screening in urban areas and attention to screening quality for dense breast tissue might be prudent.

An audit of assessment procedures in women who develop breast cancer after a negative result

Objectives: A case audit was undertaken to determine the extent to which the early diagnosis of cancer could be improved by better adherence to screening guidelines, and to estimate the effect that this might have on breast cancer survival. Although affecting only a small proportion of the cancers of the screening programme, this exercise had an educational function for screening radiologists. Setting: The East Anglian breast screening programme, a group of seven centres offering screening to a total population of 2.2 million inhabitants. Women were screened every three years between the ages of 50 and 64. Methods: Adherence to the guidelines of the UK National Breast Screening Programme (as published in 2001) was tested in women assessed between the start of screening on 1 April 1989 and 31 December 1999, in cases where the screen was negative but who were subsequently diagnosed with breast cancer. Results: In this period the programme screened 503,493 women, recalled 25,346 and diagnosed 3689 with cancer. 194 cancers in 193 women were reviewed, comprising those cancers that arose at the site of the lesion previously assessed. 96 women (49.5%) had calcifications, 48 (24.7%) had opacities. 139 of 194 cases were judged to have been inadequately assessed. A recurring theme showed that biopsies not undertaken or with false negative findings led to failure to diagnose lesions which were subsequently shown to be cancer. Microcalcifications and opacities were more likely to have been inadequately assessed than spiculate masses, parenchymal deformities, or asymmetric densities. In the earliest time period (1989–1993), there were a larger proportion of inadequately assessed cases than in the period 1994–1999. Conclusion: Scrupulous adherence to good guidelines will result in a greater proportion of cancers being diagnosed. Failure to perform effective percutaneous biopsy was the usual cause of missed diagnoses. Although an infrequent occurrence this may have an effect on subsequent survival from breast cancer.

Use of lung cancer risk models in planning research and service programs in CT screening for lung cancer.

Computed tomography screening for lung cancer is now being tested in a number of international trials. The long-term success of the approach in the future National Screening Programme is dependent upon identifying populations at sufficient risk of lung cancer that the benefit–harm ratio of the intervention is likely to be high. There are a number of lung cancer risk prediction models currently available. We review these, and demonstrate, using the Liverpool Lung Project risk prediction model as a case study, the potential for use of a risk prediction model in the design of a randomized trial of lung cancer screening and in the planning of a service screening program.