PET/CT Assessment of Estrogen Receptor positivity for Breast Cancer using [68Ga]Ga-RM2 Bombesin Receptor Antagonist: A Systematic Review and Meta-Analysis

[⁶⁸Ga]Ga-RM2 is a novel gastrin-releasing peptide receptor antagonist with emerging diagnostic utility in low-grade breast cancer (BC) expressing estrogen receptors (ER). This systematic review and meta-analysis evaluates the current diagnostic utility of [⁶⁸Ga]Ga-RM2 PET/CT and explores BC tumor uptake metrics in ER-positive BC lesions. A systematic search of PubMed, Scopus, and Web of Science databases was conducted using relevant keywords to extract, screen, and select eligible data for analysis. Out of 182 articles reviewed, only four studies were found eligible for inclusion. Qualitative data analysis was applied to four included papers meeting the eligibility criteria. Various promising utilities were identified, including [⁶⁸Ga]Ga-RM2′s ability to detect ER-positive primary BC lesions, lymph nodes, and distant metastatic lesions. Additionally, recent studies have addressed its potential for assessing therapy response following neoadjuvant chemotherapy. Importantly, [⁶⁸Ga]Ga-RM2 has demonstrated clinical utility in improving and guiding proper management planning by detecting metastatic lesions that can alter overall staging and treatment strategies. The overall lesion detectability was 93% (95% CI: 87-98%) for ER-positive BC. ER-positive BC lesions showed significantly higher maximum standardized uptake values (SUVmax) compared to ER-negative lesions, with a weighted mean difference (WMD) of 10.6 (95% CI: 8.1-13.2; P < 0.00001). Furthermore, ER-positive BC lesions exhibited statistically significant higher SUVmax compared to normal background breast tissue SUVmean, with an overall WMD of 9.9 (95% CI: 7.5-12.2; P < 0.00001). Further studies utilizing this promising radiotracer should be encouraged, implementing prospective, large-scale designs in the near future.