{
  "abstract": "ErbB2 overexpression occurs in 15-20% of invasive breast cancer (BC) and inactivation of Cyclin D1-CDK4/6 axis reduce mammary stem/progenitor cells in ErbB2-driven tumorigenesis. Here, we explored the preventive role of short-term palbociclib intervention in MMTV-ErbB2 mice. Palbociclib significantly inhibited the proliferation and stemness of ErbB2-overexpressed BC cells in vitro and in vivo. Furthermore, short-term palbociclib exposure during the early premalignant risk window significantly delayed mammary tumor development and reduced tumor multiplicity, accompanied by the suppression of epithelial proliferation and ductal/alveolar morphogenesis in premalignant tissues, as well as prolonged tumor-free survival compared with controls. Importantly, palbociclib reduced the luminal epithelial (CD24high/CD49flow), mammary reconstitution unit-enriched (CD24high/CD49fhigh) subpopulations, and luminal progenitor/TIC-enriched (CD61high/CD49fmid) subpopulations. These changes were accompanied by diminished mammary epithelial cell stemness functions, including colony-forming, mammosphere-forming, and 3D growth activities of mammary epithelial cells. Mechanistically, palbociclib-treated tissues showed inhibition of the Cyclin D1-CDK4/6-RB-E2F axis and coordinated attenuation of ER-, ErbB2- and Wnt/{beta}-catenin-associated signaling. Together, we demonstrate that short-term CDK4/6 inhibition during a premalignant risk window produces a sustained delay in ErbB2-driven mammary tumorigenesis, associated with remodeling of the mammary epithelial hierarchy and suppression of proliferative and stem/progenitor-associated activity, suggesting CDK4/6 inhibition as a strategy for ErbB2-positive BC prevention.",
  "abstract_shown": true,
  "affiliations": [
    "North Carolina Central University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "Y. Liu"
    },
    {
      "name": "A. B. Parris"
    },
    {
      "name": "Z. Ma"
    },
    {
      "name": "L. Wei"
    },
    {
      "name": "Y. Qi"
    },
    {
      "affs": [
        0
      ],
      "name": "X. Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2yyv962v4zzpg.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.14.751306",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751306v1.full",
  "id": "2yyv962v4zzpg",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751306v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2740|Advanced Breast Cancer Therapies"
    ]
  ],
  "openalex": "W7213469736",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751306v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2yyv962v4zzpg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:50Z",
      "native_id": "10.64898/2026.09.14.751306",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751306v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Risk-Window Palbociclib Exposure Delays ErbB2-Driven Mammary Tumorigenesis and Suppresses Mammary Epithelial Cell Stemness",
  "title_text": "Risk-Window Palbociclib Exposure Delays ErbB2-Driven Mammary Tumorigenesis and Suppresses Mammary Epithelial Cell Stemness",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:50Z",
  "url": "https://research.draconitic.com/paper/2yyv962v4zzpg",
  "venue": "bioRxiv",
  "versions": []
}