Application of PI3K inhibitors in breast cancer treatment: a clinical trial landscape analysis based on clinical trial databases and registries.

To characterize the clinical trial landscape of PI3K inhibitors in breast cancer and evaluate their efficacy, safety, and publication status. We searched eight major clinical trial databases using standardized MeSH/Emtree terms up to January 1, 2026. Of 283 potentially eligible studies screened independently by two reviewers, 87 trials were included for descriptive statistical analysis using R 4.5.1 and SPSS 26.0. Inter-rater agreement was assessed using Cohen's kappa. The United States led global research activity, Europe formed a collaborative network, and China and Korea emerged as important nodes in the Asia-Pacific region. Phase I trials accounted for 34.5% of included studies. PI3Kα was the predominant target (46 trials), and alpelisib was the most extensively studied agent. Marked publication bias was observed, with over 60% of trials involving key targets remaining unpublished; phase I trials had the lowest reporting rate. PI3Kα inhibitors, particularly alpelisib and inavolisib, combined with endocrine therapy improved progression-free survival in PIK3CA-mutated HR+/HER2- advanced breast cancer, while alpelisib was the only agent to demonstrate an overall survival benefit. Pan-PI3K inhibitors showed more limited efficacy and greater toxicity. Hyperglycemia and diarrhea were the most commonly reported serious adverse events. PI3Kα inhibitors show promising efficacy in PIK3CA-mutated HR+/HER2- breast cancer, but publication bias, resistance, target-specific toxicity, and geographic disparities remain major barriers. Mandatory trial reporting, biomarker-guided treatment, and international collaboration should be prioritized.