Breast cancer screening effectiveness and mortality/case-fatality burden: global associations and optimisation pathways based on GBD 2021 and CanScreen5 data

While population-based breast cancer screening (BCS) reduces breast cancer mortality in high-income settings, low- and middle-income countries (LMICs) have increased in breast cancer mortality, driven largely by severe screening inequities and late-stage diagnosis. The relationship between multidimensional BCS effectiveness and national breast cancer mortality and case-fatality outcomes across human-development strata remains poorly characterized. This study aimed to develop a comprehensive Screening Effectiveness Index (SEI), quantify global BCS inequities, and identify context-specific optimisation pathways to reduce the disproportionate breast cancer burden in LMICs.

We harmonized 2011-2021 BCS program data (including availability, coverage, and performance metrics) from the International Agency for Research on Cancer (IARC) CanScreen5 repository with age-standardized breast cancer burden estimates from the Global Burden of Disease (GBD) Study 2021 (GBD 2021), using the national female population aged 15 years and older as the denominator for all rate calculations. We included 93 countries and territories with complete core data, prioritized mortality and case fatality percentage (CFP) as primary outcomes. We used descriptive statistics and spatial analyses to quantify inequalities, generalized linear models (GLMs) to assess associations between SEI and breast cancer burden, and fuzzy-set qualitative comparative analysis (fsQCA) to identify configurations influencing SEI.

Population-based BCS programmes existed in 62 of 93 countries and territories (66.7%), almost exclusively concentrated in high- or very high-Human Development Index (HDI) settings. The global median SEI was 13.47 [interquartile range (IQR), 10.70-15.53], with a 4.5-fold difference between the highest-performing country (Netherlands: 25.24) and the lowest (Bangladesh: 5.60). Globally, each 10-point increase in SEI was independently associated with a 2.4% reduction in age-standardized mortality [β=-0.24, 95% confidence interval (CI): -0.41 to -0.07] and a 4.2% reduction in CFP (β=-0.42, 95% CI: -0.73 to -0.11), with the strongest protective effects observed in very high-HDI countries (mortality: β=-0.31, 95% CI: -0.57 to -0.05; CFP: β=-0.59, 95% CI: -0.98 to -0.20). fsQCA revealed three sufficient pathways of high SEI: economy-education-equity (EEE), economy-equality (EE1), and education-equality (EE2).

BCS inequity amplifies the global burden of breast cancer. Context-specific strategies are required: high-income countries (HICs) should optimise investment and technology, while LMICs should prioritise health education and community engagement. Future research should refine SEI determinants in resource-limited settings to enhance screening effectiveness and reduce mortality.