Background: In England, population mammographic screening has been offered to women for over 20 years. Overall decrease in breast cancer mortality rates and improvements in cancer awareness and organization of medical care over this period call for a more current evaluation of the mediators behind the better prognosis of screening-exposed breast cancers. Methods: A case-control study was conducted within the English National Breast Screening Program. Women who died from primary breast cancer in 2008 to 2009 were matched (by year of birth, screening invitation, and area) to controls that received a diagnosis of invasive breast cancer at the time of the case diagnosis but survived the case death. Data were analyzed by unconditional logistic regression with adjustment for matching factors. Results: The unadjusted OR for dying from breast cancer associated with ever having attended breast screening was 0.44 [95% confidence interval (CI), 0.33-0.58]. After adjustment for lead time, overdiagnosis, and self-selection, the OR increased to 0.69 (95% CI, 0.50-0.94). Adjusting for tumor size, lymph node status, stage, grade, histopathology, and laterality accounted for all the screening effect (OR, 1.00; 95% CI, 0.71-1.40). Further adjustment for treatment factors only had a minimal impact on the OR (OR, 1.02; 95% CI, 0.72-1.45). Conclusions: Our results suggest that earlier diagnosis, as reflected by tumor characteristics, remains the major mediator of the improvement in breast cancer survival due to participation in mammographic screening. Impact: Mammographic screening continues to prevent breast cancer-related deaths in the epoch of adjuvant systemic therapy. Cancer Epidemiol Biomarkers Prev; 25(3); 479-87.
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