Twenty Years of Macromastia Research: A Comprehensive Analysis of Diagnostic Standardization, Surgical Technique Optimization, and Exploration of Molecular Mechanisms

Macromastia, characterized by excessive breast tissue growth, causes physical symptoms, psychosocial distress, and diminished quality of life. Despite the effectiveness of reduction mammaplasty, progress remains limited by inconsistent diagnostic criteria and incomplete mechanistic understanding. We combined bibliometric analysis with transcriptomic profiling to map research evolution and identify candidate molecular pathways. Bibliometric analysis of 499 macromastia publications from the Web of Science Core Collection (Clarivate Analytics, Philadelphia, PA, USA) employed keyword co-occurrence, thematic clustering, and temporal trend analysis. Complementarily, transcriptomic sequencing was performed on breast tissue from 3 severe macromastia patients (unilateral specimen >500 g) and 4 controls undergoing mammoplasty for benign conditions, with standardized preprocessing, differential expression analysis, and functional enrichment. Bibliometric mapping revealed a paradigm shift from subjective assessments toward quantitative evaluation in diagnosis, surgical planning, and quality-of-life measurement. Emerging terms (2021-2025) including 3D imaging, digital modeling, and inframammary fold measurements reflected growing emphasis on objective standards. Core themes centered on surgical outcomes, complications, and patient satisfaction. Mechanistic keywords increasingly highlighted hormonal regulation-particularly estrogen metabolism (aromatase/CYP19A1) and prolactin-related dysfunction-alongside emerging interest in cell communication and stem cells. Transcriptomic profiling identified differential expression patterns consistent with endocrine and growth signaling, with pathway enrichment implicating immune regulation, extracellular matrix remodeling, and oxidative stress. Downregulated pathways were enriched for DNA repair and transcriptional regulation.By integrating bibliometrics with transcriptomics, this study synthesizes two decades of macromastia research, documents the transition toward quantitative standards, and nominates molecular pathways warranting further validation.