{
  "abstract": "Background: Patients with endocrine-resistant hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) have limited effective treatment options. Heat shock protein 90 (HSP90) regulates estrogen receptor stability and function; its inhibition has been proposed as a strategy to overcome endocrine resistance. Ganetespib is a second-generation HSP90 inhibitor with demonstrated anti-tumor activity in preclinical breast cancer models.\n\nMethods: In this randomized phase II study, 50 patients with HR+ MBC previously treated with endocrine therapy were randomized 1:2 to fulvestrant alone (n = 15) or fulvestrant with ganetespib (n = 35), respectively. Median age was 53 years. Fulvestrant was administered at standard dosing; ganetespib (200 mg/m2) was given intravenously on days 1, 8, and 15 of each 28-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival and safety/tolerability.\n\nResults: Median PFS was similar between arms (3.7 vs 3.6 months; log-rank P = .79). Toxicity was higher with ganetespib, with substantially increased diarrhea (97% vs 7%) and nausea (63% vs 40%). Exploratory genomic analysis of on-treatment biopsies (n = 13) showed ESR1 mutations were enriched among patients without clinical benefit, while all patients with clinical benefit exhibited a Luminal A transcriptional subtype. Tumors lacking clinical benefit showed enrichment of proliferative and cell cycle–associated transcriptional programs.\n\nConclusions: Adding ganetespib to fulvestrant did not improve clinical outcomes and increased toxicity in endocrine-resistant HR+ MBC. Our findings support the hypothesis that ESR1 alterations and proliferative transcriptional activity contribute to established endocrine resistance, limiting the therapeutic impact of HSP90 inhibition in this setting.\n\nClinical trial registration number: NCT01560416 (ClinicalTrials.gov)",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "name": "Albert Grinshpun",
      "orcid": "0000-0002-3351-5719"
    },
    {
      "name": "Adrienne G Waks"
    },
    {
      "name": "Jingxin Fu",
      "orcid": "0000-0002-4028-3661"
    },
    {
      "name": "Patrick Kurnia",
      "orcid": "0009-0009-8263-3314"
    },
    {
      "name": "Hao Guo"
    },
    {
      "name": "Tianyu Li"
    },
    {
      "name": "McKenna Moore"
    },
    {
      "name": "Molly DiLullo",
      "orcid": "0009-0005-1036-796X"
    },
    {
      "name": "Ashka Patel"
    },
    {
      "name": "Luke Whitesell",
      "orcid": "0000-0001-6445-5766"
    },
    {
      "name": "Stefan Atanasov"
    },
    {
      "name": "Ann H Partridge",
      "orcid": "0000-0002-4722-4824"
    },
    {
      "name": "Erica L Mayer",
      "orcid": "0000-0001-5430-8957"
    },
    {
      "name": "Ian E Krop",
      "orcid": "0000-0002-6380-5944"
    },
    {
      "name": "Sandro Santagata",
      "orcid": "0000-0002-7528-9668"
    },
    {
      "name": "Myles Brown",
      "orcid": "0000-0002-8213-1658"
    },
    {
      "name": "Eric P Winer"
    },
    {
      "name": "Katherine Reeder-Hayes"
    },
    {
      "name": "Carey Anders"
    },
    {
      "name": "Rinath Jeselsohn",
      "orcid": "0000-0001-7996-7529"
    },
    {
      "name": "Nancy U Lin",
      "orcid": "0000-0003-2263-5413"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fqgenwwkj93hw.bib",
  "cited_by": 0,
  "doi": "10.1093/oncolo/oyag414",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13728916/",
  "id": "fqgenwwkj93hw",
  "issns": [
    "1083-7159",
    "1549-490X"
  ],
  "landing_url": "https://doi.org/10.1093/oncolo/oyag414",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "AcademicSubjects/MED00010"
    ],
    [
      "heading",
      "Breast Cancer"
    ],
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "2730|Advanced Breast Cancer Therapies"
    ]
  ],
  "openalex": "W7221755665",
  "pdf_url": "https://academic.oup.com/oncolo/advance-article-pdf/doi/10.1093/oncolo/oyag414/71947679/oyag414.pdf",
  "pmcid": "PMC13728916",
  "pmid": "42873573",
  "published": "2026-10-14",
  "publisher": "Oxford University Press",
  "ris": "https://research.draconitic.com/paper/fqgenwwkj93hw.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:21:46Z",
      "native_id": "PMC13728916",
      "source": "pmc",
      "url": "https://doi.org/10.1093/oncolo/oyag414"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Advanced Breast Cancer Therapies",
      "subfield": "oncology"
    }
  ],
  "title": "A randomized phase II study of fulvestrant with or without ganetespib in patients with endocrine-resistant metastatic breast cancer",
  "title_text": "A randomized phase II study of fulvestrant with or without ganetespib in patients with endocrine-resistant metastatic breast cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:46Z",
  "url": "https://research.draconitic.com/paper/fqgenwwkj93hw",
  "venue": "The Oncologist",
  "versions": []
}