Background: Observational studies are necessary to assess the impact of population screening on breast cancer mortality. While some ecological studies have notably found little or no association, case-control studies consistently show strong inverse associations, but they are sometimes ignored, perhaps due to theoretical biases arising from the study design. We conducted a case-control study of breast cancer deaths in Western Australia to evaluate the effect of participation in the BreastScreen Australia program, paying particular attention to potential sources of bias, and undertook an updated meta-analysis of case-control studies.Methods: Our study included 427 cases (women who died from breast cancer), each matched to up to 10 controls. We estimated the association between screening participation and breast cancer mortality, quantifying the effect of potential sources of bias on our findings, including selection bias, information bias, and confounding. We also conducted a meta-analysis of published case-control studies.Results: The OR for participation in the Western Australian BreastScreen program in relation to death from breast cancer was 0.48 [95% confidence interval (CI), 0.38-0.59; P < 0.001]. We were unable to identify biases that could negate this finding: sensitivity analyses generated ORs from 0.45 to 0.52. Our meta-analysis yielded an OR of 0.51 (95% CI, 0.46-0.55).Conclusions: Our findings suggest an average 49% reduction in breast cancer mortality for women who are screened. In practice, theoretical biases have little effect on estimates from case-control studies.Impact: Case-control studies, such as ours, provide robust and consistent evidence that screening benefits women who choose to be screened. Cancer Epidemiol Biomarkers Prev; 21(9); 1479-88. Ó2012 AACR.

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The aim of this study was to optimise the experimental protocol and data analysis for in-vivo breast cancer x-ray imaging. Results are presented of the experiment at the SYRMEP beamline of Elettra Synchrotron using the propagation-based phase-contrast mammographic tomography method, which incorporates not only absorption, but also x-ray phase information. In this study the images of breast tissue samples, of a size corresponding to a full human breast, with radiologically acceptable x-ray doses were obtained, and the degree of improvement of the image quality (from the diagnostic point of view) achievable using propagation-based phase-contrast image acquisition protocols with proper incorporation of x-ray phase retrieval into the reconstruction pipeline was investigated. Parameters such as the x-ray energy, sample-to-detector distance and data processing methods were tested, evaluated and optimized with respect to the estimated diagnostic value using a mastectomy sample with a malignant lesion. The results of quantitative evaluation of images were obtained by means of radiological assessment carried out by 13 experienced specialists. A comparative analysis was performed between the x-ray and the histological images of the specimen. The results of the analysis indicate that, within the investigated range of parameters, both the objective image quality characteristics and the subjective radiological scores of propagation-based phase-contrast images of breast tissues monotonically increase with the strength of phase contrast which in turn is directly proportional to the product of the radiation wavelength and the sample-to-detector distance. The outcomes of this study serve to define the practical imaging conditions and the CT reconstruction procedures appropriate for low-dose phase-contrast mammographic imaging of live patients at specially designed synchrotron beamlines.