PS5-11-07: The Global Landscape of Practice-Changing Breast Cancer De-Escalation Randomized Trials

Abstract Introduction Breast cancer (BC) treatment de-escalation aims to reduce treatment morbidity without compromising oncologic outcomes. Several trials have evaluated surgery, radiation, and systemic therapy de-escalation, but their global distribution and downstream clinical impact have not been described. We hypothesized that the U.S. lags other regions in leading BC de-escalation trials, and that geography, sponsorship, journal impact factor (IF), and intervention discipline influence clinical adoption. Methods We conducted a systematic review of published randomized prospective BC de-escalation trials from 1975 to 2024 following PRISMA guidelines. PubMed, Embase, Scopus, and major clinical guidelines (NCCN, ASCO, ESMO, ASTRO, St. Gallen) were queried. We collected trial characteristics, authorship geography, funding source, and 2023 journal IF. A practice-changing designation was defined by its adoption in clinical guidelines, explicit statements in high-impact publications, or real-world adoption evidence. Historic guideline citation was assessed via the Internet Archive’s Wayback Machine. Statistical tests, temporal trends, and multivariable regression were utilized to identify predictors of practice-changing status and guideline citation. Covariates included publication year, U.S. versus non-U.S. origin, intervention type, sponsor, journal IF, pharma involvement, and multi-center design. Results We included 127 randomized prospective trials. 82.7% were multi-center, 53.5% focused on radiation de-escalation, 23.6% on surgery, and 22.0% on systemic therapy. Publications span 1985-2024, with a marked rise in the 2010s (47.2%) and 2020s (36.2%), compared to 15.0% in the 2000s and <1% each in the 1980s and 1990s (p < 0.001). The share of U.S.-led de-escalation trials declined steadily over time, as non-U.S. activity rose worldwide. Of all trials, 21.3% were U.S.-based, and this proportion dropped from 100% in the 1980s to 14.0% in the 2020s. Among all studies, 58.3% were classified as practice-changing based on adoption in guidelines or clinical uptake. Guideline citation rates were 33.9% for NCCN, 22.8% for St. Gallen, 15.0% for ESMO, 12.6% for ASTRO, and 6.3% for ASCO. Only NCCN demonstrated a significant regional bias favoring U.S. trials (p = 0.0141); no such preference was observed in other guideline bodies. Geographically, most studies were led by European investigators (66.1%), followed by North America (25.2%) and Asia (8.7%). U.S.-based studies most often focused on surgical de-escalation (44.4%), while non-US trials more frequently addressed radiation (60.0%). US trials were more likely to appear in high-impact journals (mean IF: 54.4 vs. 34.5), which may partially explain their higher but not statistically significant practice-changing rate (74.1% vs. 54.0%, p = 0.0975). Among 74 practice-changing trials, those published in high-impact journals (IF ≥10) were more likely to be cited in guidelines (OR = 3.38, 95% CI: 1.47-8.04, p = 0.005). In contrast, U.S. origin was not a significant predictor of practice-changing status (OR = 1.15, p = 0.795). Publication year was consistently associated with decreased odds of downstream influence: each year after 2010 was linked to lower odds of practice-changing designation (OR = 0.84, p < 0.001) and guideline citation (OR = 0.86, p < 0.001). Conclusion Our study highlights global research on BC de-escalation, with most modern trials led by non-U.S. investigators. Although U.S.-based trials were more often labeled practice-changing, geographic origin did not independently predict inclusion in guidelines. Instead, publication in high-impact journals was the strongest predictor of downstream influence. U.S.-led de-escalation trials declined to 14% in the 2020s, which suggests a shifting center of gravity in BC de-escalation research. Citation Format: L. M. Adwer, C. E. Dougherty, J. I. Orozco, J. A. Santamaria-Barria. PS5-11-07: The Global Landscape of Practice-Changing Breast Cancer De-Escalation Randomized Trials [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-11-07.