Araujo Carolina Fumico Massuda, Nunes Lélia Cápua, Murta-Nascimento Cristiane, Bragagnoli Arinilda Campos, Fukushima Fernanda Bono, de Pádua Souza Cristiano, de Oliveira Vidal Edison Iglesias
Public Health Department, Medical School, São Paulo State University (UNESP), Botucatu, SP, Brazil.
Medicine Department, Science of Life Institute, Juiz de Fora - Campus Governador Valadares Federal University (UFJF-GV), Governador Valadares - MG, Brazil.
BMC Cancer. 2025 Aug 21;25(1):1352. doi: 10.1186/s12885-025-14468-3.
Metformin has been the focus of substantial interest in the field of oncology. Although breast cancer is the type of cancer where metformin was most extensively studied through randomized clinical trials (RCTs), none of the previous reviews in this field provided a comprehensive overview of the landscape of RCTs taking into account the phenotype of breast cancer, its staging, and treatment modalities. This scoping review sought to comprehensively map the literature of RCTs focusing on the use of metformin in the treatment of breast cancer and followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Extension for Scoping Reviews guidelines. The eligibility criteria encompassed all RCTs involving metformin for adult patients with breast cancer, with no constraints regarding context, language, publication date, or outcomes. We included 122 reports from 40 RCTs comprising a total of 5,623 participants and 107 distinct outcomes. The results showed that most studies did not present results by phenotype of breast cancer and highlighted critical gaps and opportunities in the literature. Notably, limited evidence from subgroup analyses within a large RCT suggested potential benefits of metformin in improving overall and disease-free survival among HER2 + participants but not among patients with other phenotypes, a result that requires further investigation. Our findings highlight the potential for considerably expanding the current knowledge base in this field through the retrospective determination of participant phenotypes, facilitating cost-effective and time-efficient individual participant data meta-analyses. Furthermore, we recommend that funding agencies and journals mandate the comprehensive presentation of results from RCTs on breast cancer based on phenotype.
二甲双胍一直是肿瘤学领域大量研究的焦点。尽管乳腺癌是通过随机临床试验（RCT）对二甲双胍进行最广泛研究的癌症类型，但该领域此前的综述均未在考虑乳腺癌表型、分期及治疗方式的情况下，对RCT的整体情况进行全面概述。本范围综述旨在全面梳理聚焦于二甲双胍治疗乳腺癌的RCT文献，并遵循系统评价与Meta分析的首选报告项目（PRISMA）扩展版范围综述指南。纳入标准涵盖所有涉及成年乳腺癌患者使用二甲双胍的RCT，对研究背景、语言、发表日期或结果均无限制。我们纳入了40项RCT的122份报告，共计5623名参与者及107种不同的结果。结果显示，大多数研究未按乳腺癌表型呈现结果，并突出了文献中的关键差距与机遇。值得注意的是，一项大型RCT中的亚组分析证据有限，提示二甲双胍可能对HER2阳性参与者改善总生存期和无病生存期有益，但对其他表型患者无此作用，这一结果需要进一步研究。我们的研究结果强调，通过回顾性确定参与者表型，有潜力大幅扩展该领域当前的知识库，促进具有成本效益和时间效率的个体参与者数据Meta分析。此外，我们建议资助机构和期刊要求基于表型全面呈现乳腺癌RCT的结果。
