{
  "abstract": "Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become cornerstone therapeutics for type 2 diabetes mellitus and obesity, but their impact on breast cancer remains uncertain. Preclinical studies show context-dependent effects of GLP-1 RAs on breast-cancer cells. Direct evidence from breast-cancer models supports a pro-proliferative NADPH oxidase 4 (NOX4)/reactive oxygen species (ROS) /VEGF pathway under supra-pharmacological exposure, whereas PI3K/Akt-mediated pro-survival signaling and cAMP/PKA/CREB-driven proliferation remain inferred from non-breast systems and require direct confirmation. Under obesity- and insulin-resistant conditions, indirect antitumor effects may occur through improved insulin sensitivity, altered adipokines, and remodeling of the tumor immune microenvironment. Meta-analyses of randomized controlled trials do not show a significant increase in breast-cancer risk (RR 0.98, 95% CI 0.76-1.26), while some large observational cohorts report small risk differences that are susceptible to confounding and detection bias. Evidence for inter-agent differences is observational and limited by the absence of head-to-head randomized oncological comparisons. This narrative review synthesizes preclinical and clinical evidence across three dimensions, namely, molecular subtype, drug exposure, and host metabolic status, and distinguishes direct breast-cancer evidence from mechanistic extrapolation. We outline evidence-informed clinical considerations and research priorities rather than definitive recommendations.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical Laboratory, The Central Hospital of Qinghe County",
    "Department of Pathogen Biology, Guizhou Nursing Vocational College",
    "Department of Clinical Laboratory, Zunyi Hospital of Traditional Chinese Medicine",
    "Medical Affairs Department, The Second Affiliated Hospital of Zunyi Medical University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhen-yu Xie"
    },
    {
      "affs": [
        1
      ],
      "name": "Yue Qian"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Ting-ting Liu"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Ping Xiang"
    },
    {
      "affs": [
        2
      ],
      "name": "Ying Mu"
    },
    {
      "affs": [
        3
      ],
      "name": "Wei Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fgk41zqxdqz4d.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1978397",
  "fulltext_url": null,
  "id": "fgk41zqxdqz4d",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1978397/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Metabolism, Diabetes, and Cancer"
    ]
  ],
  "openalex": "W7224131395",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1978397/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/fgk41zqxdqz4d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1978397",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1978397/full"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Metabolism, Diabetes, and Cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Context-dependent pharmacological effects of GLP-1 receptor agonists in breast cancer from molecular mechanisms to clinical safety",
  "title_text": "Context-dependent pharmacological effects of GLP-1 receptor agonists in breast cancer from molecular mechanisms to clinical safety",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/fgk41zqxdqz4d",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}