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乳腺癌中的胰高血糖素样肽-1受体激动剂:肥胖与预后管理的新前沿

GLP-1 Receptor Agonists in Breast Cancer: A New Frontier in Obesity and Prognosis Management.

作者信息

Xande Juliana G, Del Giglio Auro

机构信息

Department of Oncology, Centro Universitário Faculdade de Medicina do ABC (FMABC), Avenida Príncipe de Gales 821, Santo André 09060-650, SP, Brazil.

出版信息

Int J Mol Sci. 2025 Aug 11;26(16):7744. doi: 10.3390/ijms26167744.

Abstract

Obesity is a well-established risk factor for both the incidence and poorer clinical outcomes of Breast Cancer (BC), particularly among hormone receptor-positive postmenopausal women. However, conventional weight loss interventions have yielded limited success in altering cancer prognosis. Recently, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide and tirzepatide, have emerged as effective pharmacologic agents for sustained weight loss and are under investigation in oncology. This narrative review synthesizes evidence linking obesity to poor BC prognosis and evaluates the therapeutic potential of GLP-1 RAs in this context. Mechanistically, obesity exacerbates tumor progression through hormonal imbalance, chronic inflammation, and adipokine and insulin signaling, targets that may be modifiable through weight reduction. GLP-1 RAs offer multiple benefits, such as appetite suppression, delayed gastric emptying, and enhanced insulin sensitivity. Clinical studies in BC patients have shown weight loss ranging from 2.3% to 5%, likely attenuated by concurrent endocrine therapy. Preliminary data suggest that GLP-1 RA use does not increase the risk of cancer recurrence and may reduce cardiovascular morbidity. However, prospective studies are needed to confirm long-term oncologic safety and efficacy. Disparities in access and cost remain barriers to widespread adoption. Nevertheless, GLP-1 RAs represent a promising adjunct to manage obesity among BC patients, potentially improving metabolic health and long-term cancer outcomes.

摘要

肥胖是乳腺癌(BC)发病及临床预后较差的一个公认风险因素,在激素受体阳性的绝经后女性中尤为如此。然而,传统的减肥干预措施在改变癌症预后方面成效有限。最近,胰高血糖素样肽-1受体激动剂(GLP-1 RAs),如司美格鲁肽和替尔泊肽,已成为实现持续减肥的有效药物,并正在肿瘤学领域进行研究。这篇叙述性综述综合了将肥胖与BC预后不良联系起来的证据,并评估了GLP-1 RAs在这种情况下的治疗潜力。从机制上讲,肥胖通过激素失衡、慢性炎症以及脂肪因子和胰岛素信号传导加剧肿瘤进展,而这些靶点可能通过减轻体重来改变。GLP-1 RAs具有多种益处,如抑制食欲、延迟胃排空和增强胰岛素敏感性。对BC患者的临床研究表明体重减轻幅度在2.3%至5%之间,可能因同时进行的内分泌治疗而减弱。初步数据表明,使用GLP-1 RA不会增加癌症复发风险,可能还会降低心血管疾病发病率。然而,需要前瞻性研究来证实其长期肿瘤学安全性和疗效。获取途径和成本方面的差异仍然是广泛应用的障碍。尽管如此,GLP-1 RAs是管理BC患者肥胖的一种有前景的辅助手段,可能改善代谢健康和长期癌症预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1590/12386789/8adf7e9ea708/ijms-26-07744-g001.jpg

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