Global Burden and Risk Factors of Breast Cancer in Female Adolescents and Young Adults, 1990-2021: Results from the Global Burden of Disease Study 2021

Background: Breast cancer in female adolescents and young adults [(AYAs); aged 15-39 years] is biologically distinct from breast cancer with later onset, exhibiting aggressive histomolecular features and poorer survival. Despite its substantial clinical and societal impact, comprehensive global estimates of the burden specific to female AYAs, temporal trends, and attributable risk factors remain limited, as most studies aggregate data across broad age ranges. Aims: To quantify the global, regional, and national burden of breast cancer among female AYAs from 1990 to 2021; examine trends stratified by sociodemographic index (SDI) and age subgroup; and assess risk-attributable disability-adjusted life years (DALYs) within the Global Burden of Disease (GBD) comparative risk assessment framework. Study Design: Secondary analysis of modeled estimates from the GBD Study 2021, covering 204 countries and territories. Methods: We extracted female-specific, age-specific incidence, mortality, and DALY counts and rates for AYA breast cancer from the GBD 2021 database. Age-standardized incidence (ASIR), mortality (ASMR), and DALY (ASDR) rates per 100,000 females were calculated using the GBD world standard population weights, renormalized across the five AYA age groups. Temporal trends from 1990 to 2021 were assessed using Joinpoint regression, and average annual percentage changes (AAPCs) were used to describe the direction and magnitude of the trends. Stratified analyses were performed by SDI quintile (high, high-middle, middle, low-middle, and low) and five-year age group (15-19 to 35-39 years). Results: Globally, among female AYAs, the ASIR increased steadily from 8.86 (95% UI, 8.51-9.21) per 100,000 females in 1990 to 11.73 (95% UI, 11.14-12.31) in 2021, with an AAPC of 0.91%, whereas the ASMR and ASDR initially declined before reversing direction and increasing in recent years. By SDI quintile, the ASIR increased in the low, low-middle, middle, and high-middle SDI quintiles; the high SDI quintile showed no clear overall trend but a modest decline from 2016 to 2021. The ASMR and ASDR declined in high and high-middle SDI countries (e.g., AAPC for ASMR in the high SDI quintile, -1.60%) but increased in low-middle and low SDI countries (e.g., AAPC for ASMR in the low-middle SDI quintile, 1.24%). Among the 158 locations with at least 200,000 women aged 15-39 years, Türkiye had the highest AAPC point estimates for the ASIR, ASMR, and ASDR, although this finding was sensitive to the starting year, possibly reflecting limited GBD inputs before 2000. Age-stratified analyses identified the highest burden in the 35-39-year subgroup, whereas the steepest increases occurred in younger AYA age groups. Among risk-attributable DALYs, three risk factors had 95% UIs that excluded the null globally: high alcohol use, low physical activity, and smoking. Of these, only high alcohol use and smoking received a two-star rating in the GBD evidence grading system. Conclusion: The global burden of breast cancer among female AYAs has continued to rise, with persistent and widening socioeconomic disparities and an increasing concentration of the burden in less advantaged settings. Addressing these inequities will require equitable access to diagnosis and treatment in these settings.