{
  "abstract": "Pretreatment predictors of neoadjuvant chemotherapy (NAC) response are lacking, especially in ER-positive/HER2-negative breast cancer, where cytotoxic benefit is most uncertain. From 1,158 transcription-factor regulons across five discovery cohorts, we derived SensReg, a locked 13-regulon logistic signature of chemotherapy sensitivity applied without refitting. SensReg was evaluated across 40 chemotherapy-only NAC datasets (n = 3,852, mean AUROC = 0.72), of which 39 (n = 3,840) were meta-analyzable (pooled AUROC 0.72, 95% CI 0.69–0.75), including 35 validation datasets independent of discovery (n = 3,092), of which 34 (n = 3,080, mean AUROC = 0.71) contributed to the pooled validation meta-analysis (pooled AUROC 0.70, 95% CI 0.67–0.73), and 20 HER2-antibody treatment arms from 17 series (pooled AUROC 0.66, 95% CI 0.60–0.72), outperformed 17 established signatures, and showed the strongest independent association with response after multivariable adjustment, the only signature significant at BH-FDR < 0.001 (adjusted OR 1.81, 95% CI 1.57–2.09; BH-FDR = 6.3×10⁻¹⁵), although this mutually adjusted comparison is exploratory because of limited events relative to the number of predictors. It provided positive estimated net benefit in ER-positive/HER2-negative disease (22 cohorts, n = 1,228) and retained discrimination within the recurrence-score intermediate stratum (AUROC 0.735). SensReg shows no detectable prognostic signal in a treatment-naive cohort but was associated with endocrine resistance and was carried mainly by malignant epithelium within immune-engaged microenvironments, associating with favorable chemotherapy-treated outcomes. SensReg is an interpretable, transferable predictor of treatment response warranting prospective evaluation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "name": "Bashir Lawal"
    },
    {
      "name": "Xiaosong Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/feknwkek633vj.bib",
  "cited_by": 0,
  "doi": "10.21203/rs.3.rs-11001123/v1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13734259/",
  "id": "feknwkek633vj",
  "issns": [
    "2693-5015"
  ],
  "landing_url": "https://doi.org/10.21203/rs.3.rs-11001123/v1",
  "language": "en",
  "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": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1306|Breast Cancer Treatment Studies"
    ]
  ],
  "openalex": "W7224105280",
  "pdf_url": null,
  "pmcid": "PMC13734259",
  "pmid": "42990800",
  "published": "2026-10-28",
  "publisher": "American Journal Experts",
  "ris": "https://research.draconitic.com/paper/feknwkek633vj.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:23:53Z",
      "native_id": "PMC13734259",
      "source": "pmc",
      "url": "https://doi.org/10.21203/rs.3.rs-11001123/v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Breast Cancer Treatment Studies",
      "subfield": "oncology"
    }
  ],
  "title": "SensReg: A Regulon-Based Predictor of Neoadjuvant Chemotherapy Response in ER- Positive/HER2-Negative Breast Cancer",
  "title_text": "SensReg: A Regulon-Based Predictor of Neoadjuvant Chemotherapy Response in ER- Positive/HER2-Negative Breast Cancer",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:53Z",
  "url": "https://research.draconitic.com/paper/feknwkek633vj",
  "venue": "Research Square",
  "versions": []
}