Global, Regional, and National Burden of Early-Onset Breast Cancer in Women, 1990–2021: GBD 2021 Analysis of Trends, Modifiable Risk Factors, and Health Inequalities

Xingtong Zhou,1,* Xiaoying Zhong,1,* Mohan Liu,1,* Jia Liu,1 Zhongyu Luo,2 Ying Xu,1 Qiang Sun,1 Yidong Zhou11Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Orthopedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Xu; Yidong Zhou, Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China, Tel +86-010-69158720, Email [email protected]; [email protected]: Early-onset breast cancer (EOBC) affects women aged 15– 44 years during reproductive and economically active life stages. We quantified global, regional, and national EOBC burden from 1990 to 2021, including temporal inflection points, modifiable risks, and health inequalities.Methods: Using Global Burden of Disease (GBD) 2021 estimates for 204 countries and territories, we analyzed incidence, prevalence, mortality, and disability-adjusted life years (DALYs) among women aged 15– 44 years as age-standardized rates. Joinpoint regression estimated annual and average percent changes (APCs, AAPCs); population attributable fractions (PAFs) and the Socio-demographic Index (SDI) characterized risk-factor burden and inequalities.Results: In 2021, an estimated 344,924 EOBC cases occurred globally (age-standardized incidence rate: 9.63 per 100,000). Incidence increased (AAPC: +0.81%), while global mortality changed little. Joinpoint regression identified an acceleration in prevalence growth after 2012 (APC +1.62%). Among SDI strata, Low-middle SDI regions increased fastest (AAPC: +2.25%); geographically, North Africa and the Middle East (+2.90%) and South Asia (+2.44%) led the increases. Mortality declined in high-SDI regions (− 1.80%) but rose in low-middle-SDI regions (+1.15%), reflecting persistent inequalities. Incidence rose in all three age strata, fastest at 40– 44 years (AAPC +0.96% vs +0.70% and +0.30%), and only that band showed a rising DALY trend. High fasting plasma glucose, smoking, and alcohol use were the leading attributable risks; high body mass index showed negative PAFs in some high-SDI regions, a model-based signal rather than a protective effect, and its crude ecological association did not persist after adjustment for SDI.Conclusions: The burden of EOBC is increasing across the age range, with the steepest growth in regions undergoing demographic, reproductive, and lifestyle transitions. These findings support age-sensitive prevention, clearer surveillance, and equitable access to timely diagnosis and multidisciplinary care.Keywords: early-onset breast cancer, women’s health, global burden of disease, modifiable risk factors, health inequalities