{
  "abstract": "Given the heterogeneity of HER2-positive breast cancer, reliable biomarkers to guide treatment are needed. We conducted multi-platform biomarker analyses of baseline tumor tissue from the DAPHNe trial of neoadjuvant paclitaxel/trastuzumab/pertuzumab (THP) for HER2-positive early breast cancer to characterize inter- and intra-tumor heterogeneity and to identify molecular predictors of response. A total of 98 patients with stage II-III HER2-positive breast cancer received neoadjuvant THP followed by surgery. Gene expression profiling, spatial protein profiling, and single-cell imaging (cyclic immunofluorescence) were performed on pre-treatment biopsies and a subset of residual disease specimens. Pathologic response was assessed using the residual cancer burden (RCB) score. Among HER2-positive patients included in the biomarker analysis, 34% of patients had node-positive breast cancer, and 66% had hormone receptor (HR)-positive tumors. HR-positive and HR-negative tumors differed significantly across gene expression, protein expression, and single-cell profiling. High ERBB2 gene signature, p53 gene signature, and HER2 protein expression predicted favorable response (RCB 0/1), while ESR1/PGR gene, estrogen receptor (ER) signaling gene signature, and ER alpha protein expression were associated with unfavorable response (RCB 2/3). Single-cell spatial analysis revealed that cancer cells clustered by shared HER2, ER, and PR expression, suggesting local expansion of phenotypically distinct subpopulations. ER-positive cancer cells were associated with lower HLA-A and PD-L1 expression, suggesting a less immunologically active tumor cell state. Baseline HER2 and ER expression are key predictors of response to neoadjuvant HER2-targeted therapy. Single-cell spatial profiling highlights intra-tumoral heterogeneity and suggests ER-driven immune exclusion as a potential mechanism of resistance.",
  "abstract_shown": true,
  "affiliations": [
    "Dana-Farber Cancer Institute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 28,
  "authors": [
    {
      "name": "E. Chen"
    },
    {
      "name": "I. Schlam"
    },
    {
      "name": "K. Shimada"
    },
    {
      "name": "T. Li"
    },
    {
      "name": "E. R. Ogayo"
    },
    {
      "name": "A. Patel"
    },
    {
      "name": "J. Davis"
    },
    {
      "name": "J.-R. Lin"
    },
    {
      "name": "A. Schultz"
    },
    {
      "name": "M. G. Townsend"
    },
    {
      "name": "K. F. Zheng"
    },
    {
      "name": "C. W. Wanderley"
    },
    {
      "name": "R. Pastorello"
    },
    {
      "name": "F. New"
    },
    {
      "name": "E. Metzger"
    },
    {
      "name": "N. Sinclair"
    },
    {
      "name": "L. M. Spring"
    },
    {
      "name": "M. Faggen"
    },
    {
      "name": "M. Constantine"
    },
    {
      "name": "N. Desai"
    },
    {
      "name": "N. Tung"
    },
    {
      "name": "N. Tayob"
    },
    {
      "name": "I. E. Krop"
    },
    {
      "name": "S. M. Tolaney"
    },
    {
      "name": "E. P. Winer"
    },
    {
      "name": "J. L. Guerriero"
    },
    {
      "name": "E. A. Mittendorf"
    },
    {
      "affs": [
        0
      ],
      "name": "A. G. Waks"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8z6md919acmwq.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.17.752407",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752407v1.full",
  "id": "8z6md919acmwq",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752407v1",
  "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",
      "2730|HER2/EGFR in Cancer Research"
    ]
  ],
  "openalex": "W7213555337",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752407v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8z6md919acmwq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:06Z",
      "native_id": "10.64898/2026.09.17.752407",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752407v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Spatial/molecular heterogeneity and treatment response in HER2+ early breast cancer: Translational analyses from the DAPHNe trial",
  "title_text": "Spatial/molecular heterogeneity and treatment response in HER2+ early breast cancer: Translational analyses from the DAPHNe trial",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:06Z",
  "url": "https://research.draconitic.com/paper/8z6md919acmwq",
  "venue": "bioRxiv",
  "versions": []
}