Detection Strategies for HER2 and miR-21 in Breast Cancer: Current Approaches and Future Perspectives- Hybrid Systematic Review and Bibliometric Mapping

Background/Objectives: Breast cancer is still one of the main causes of mortality and morbidity at a global level, highlighting the need to identify robust biomarkers for early diagnosis, prognostic stratification and optimization of therapeutic decisions. Among these biomarkers, HER2 (Human Epidermal Growth Factor Receptor 2) and miR-21 represent the complementary levels of tumor biology, reflecting oncogenic signaling at the protein level and post-transcriptional regulation of gene expression. This hybrid systematic review and bibliometric mapping aims to critically analyze current methods for determining HER2 and miR-21 biomarkers, highlighting their advantages, limitations and clinical applicability, as well as future development directions in the field of precision oncology diagnostics. Methods: The bibliometric analyses were performed to investigate the intellectual structure, research trends, and collaboration patterns within the field of HER2 and miR-21 detection in breast cancer. A PRISMA-guided literature search was conducted in the Web of Science Core Collection (WoSCC), PubMed, and Scopus. After duplicate removal, screening, and eligibility assessment, 305 publications were included in the final review corpus. Bibliometric analyses of these 305 publications were performed using VOSviewer to investigate publication output, keyword co-occurrence, co-authorship, and institutional and country collaboration patterns. Results: Bibliometric analyses revealed the intellectual structure, research trends, and collaboration patterns within the field of HER2 and miR-21 detection in breast cancer. This work highlights the complementary role of HER2 and miR-21 biomarkers in breast cancer, highlighting their fundamental differences, but also their synergistic potential in clinical practice and translational research. A comparative analysis of detection methods highlights that, although conventional techniques remain the clinical standard, they are increasingly complemented by advanced technologies, such as digital PCR, optical and electrochemical biosensors. Conclusions: The emerging detection methods offer significant advantages in terms of sensitivity, rapidity and potential for miniaturization, but their clinical implementation is still limited by the lack of standardization and large-scale validation. A major bibliometric insight is the evident shift in publication output by country toward Asia, particularly China, India, and Iran, which currently show high publication output and extensive collaborative connectivity in the analyzed network. However, challenges remain in standardizing microRNA methods and the clinical validation of emerging technologies.