Abstract PS4-09-04: Global disparities in breast cancer clinical trials and their impact on clinical evidence, driven by underrepresentation of low- and middle-income countries

Abstract Background: Breast Cancer (BC) remains a major health challenge globally and with higher mortality in low/medium- income countries (LMIC). Generalizability of evidence from clinical trial (CT) depends on many factors, one of which is selection and recruitment of representative population. Most CT sites are in high-income countries (HICs) which creates unfair generalization as there are unique challenges for patients in LMIC including disease presentation, genetics, comorbidity, lifestyle, resources etc. We evaluated disparity in global distribution of BC CTs and contribution to clinical guidelines based on country’s economic status and geography. Methods: We searched ClinicalTrials.gov (NCT) to identify BC CTs between 2000-23. Search strategy was developed by a medical librarian. World Bank country's income level classification 2022-23 was used to classify the countries into HIC, LMIC and 7 geographic regions. CTs with at least 1 site in LMIC were qualified as LMIC CT. Data regarding CT phase, funding, design, sites were extracted. Contribution to medical evidence was quantified based on reference of CT in BC-NCCN guideline. Pearson chi-square tests used for comparison of categorical data. Results: We identified 5518 eligible BC CTs in the database. 1,630 (29.5%) trials had at least one site in LMICs compared to 4505 (81.6%) trials in HICs. Only 19.7% (86.0% in HIC) of phase 1, 27.2% (82.3% in HIC) of phase 2, 50.7% (73.4% in HIC) phase 3 had a site in LMIC countries (p < 0.01). Industrial funding was the most common source of funding for LMIC (55.4% vs 35.2% for HIC) compared to academic funding for HIC (56.6 % vs 19.8 % for LMIC, p < 0.01). 906 (55.6%) of LMICs CTs were randomized allocation compared to 1664 (36.9%, p < 0.01) for HIC. Proportion of CTs in LMIC increased from 14.1% in 2000 to 43.2% in 2023 with most significant increase in East Asia Pacific (EAP) region from 2.4% in 2000 to 39.1% in 2023, whereas it remains almost constant for South Asia (SA) (7.1% to 6.4%), Sub Saharan Africa (AFR) (2.4% to 3.2%), Latin America (LA) (8.2% to 8.9%). Proportion of CTs in North American (NA) sites decreased from 70.6% to 49.6% and were driven by increasing number of EAP CTs (4% vs 60.3% of non-NA CTs).173 CTs were referenced in BC-NCCN guidelines, 148 were registered in NCT. 92/148 were done after 2000. 64 (69.5%) included LMIC site compared 86 (93.5%, p < 0.01) for HIC. Only 43 (46.7%) in SA, 46 (50%) EAP, 15 (16.3%) in AFR, 57 (62%) LA, compared to 77 (83.7%) in Europe/Central Asian and 71 (77%) in NA. 78 (84.8%) were phase 3, 83 (90.2%) were randomized, 54 (58.7%) were industry sponsored. Conclusions: LMIC continues to be markedly underrepresented in BC CTs leading to inequity/disparity in medical evidence. Studies in the future should aim to ensure fair representation of the LMIC, so that we have improved/reliable evidence for the use of guideline-based treatment in these populations. Citation Format: V. Gupta, V. Singh, M. Alharbi, N. Sharma, L. Alessi, A. Roy, S. Gandhi, S. Kabraji. Global disparities in breast cancer clinical trials and their impact on clinical evidence, driven by underrepresentation of low- and middle-income countries. [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 PS4-09-04.