{
  "abstract": "Plasma cell-free DNA (cfDNA) is a sensitive, noninvasive tool for monitoring the genomic landscape, heterogeneity, and evolution of cancer, aggregating genetic information from multiple metastatic sites. Here, we study 15,564 cfDNA samples from 12,827 patients with metastatic breast cancer (MBC). We classify samples, deep-sequenced with Guardant360, into MBC subtypes using our trained random forest model. Most patients have variants associated with therapeutic resistance and targetability of approved and experimental therapies, including in PIK3CA, ESR1, PTEN, and AKT1. Frequencies of multiple actionable alterations differed from primary disease, and multiple variants per gene suggest independent resistant clones. The large cohort size enables uncovering clonal co-behaviors, including co-existence and exclusivity of alleles and correlation of allele fractions. cfDNA testing is now recommended in multiple advanced malignancies, including eligibility assessment for clinical trials. We envision this large collection of MBC cfDNA data as an invaluable resource for the design and planning of future clinical trials.",
  "abstract_shown": true,
  "affiliations": [
    "Broad Institute of MIT and Harvard, Cambridge, MA, USA.",
    "Department of Medicine, Boston University, Boston, MA, USA.",
    "Harvard Medical School, Boston, MA, USA.",
    "Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.",
    "Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.",
    "Guardant Health, Palo Alto, CA, USA.",
    "Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.",
    "Washington University in St Louis, St Louis, MO, USA.",
    "Department of Medicine, University of Udine, Udine, Italy.",
    "Department of Medical Oncology, CRO di Aviano, National Cancer Institute, IRCCS, Aviano, Italy.",
    "Northwestern University, Chicago, IL, USA.",
    "Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.",
    "University of Pittsburgh, Pittsburgh, PA, USA.",
    "Baylor University Medical Center, Texas Oncology, Dallas, TX, USA.",
    "Weill Cornell Medicine, New York, NY, USA.",
    "UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA. ABardia@mednet.ucla.edu.",
    "Broad Institute of MIT and Harvard, Cambridge, MA, USA. gadgetz@broadinstitute.org.",
    "Harvard Medical School, Boston, MA, USA. gadgetz@broadinstitute.org.",
    "Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA. gadgetz@broadinstitute.org.",
    "Department of Pathology, Massachusetts General Hospital, Boston, MA, USA. gadgetz@broadinstitute.org."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ignaty Leshchiner",
      "orcid": "0000-0001-8942-9265"
    },
    {
      "affs": [
        0,
        2,
        3,
        4
      ],
      "name": "Arielle J Medford"
    },
    {
      "affs": [
        0
      ],
      "name": "Justin Cha",
      "orcid": "0000-0001-6026-2211"
    },
    {
      "affs": [
        5
      ],
      "name": "Lesli A Kiedrowski",
      "orcid": "0000-0001-5081-2005"
    },
    {
      "affs": [
        4,
        6
      ],
      "name": "Andrzej Niemierko"
    },
    {
      "affs": [
        4
      ],
      "name": "Jennifer C Keenan"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Charles S Dai"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Laura M Spring",
      "orcid": "0000-0001-8904-3514"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Beverly Moy",
      "orcid": "0000-0003-3472-1140"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Seth A Wander"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Neelima Vidula"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Steven J Isakoff",
      "orcid": "0000-0002-6677-1014"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Dejan Juric",
      "orcid": "0000-0003-2983-7704"
    },
    {
      "affs": [
        0
      ],
      "name": "Mendy Miller"
    },
    {
      "affs": [
        7
      ],
      "name": "Andrew A Davis"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Lorenzo Gerratana"
    },
    {
      "affs": [
        10
      ],
      "name": "Ami Shah"
    },
    {
      "affs": [
        11
      ],
      "name": "Ben H Park",
      "orcid": "0000-0001-8119-2291"
    },
    {
      "affs": [
        12
      ],
      "name": "Adam Brufsky",
      "orcid": "0000-0001-8080-7960"
    },
    {
      "affs": [
        13
      ],
      "name": "Joyce O'Shaughnessy"
    },
    {
      "affs": [
        5
      ],
      "name": "Rebecca J Nagy"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Leif W Ellisen",
      "orcid": "0000-0003-0444-7910"
    },
    {
      "affs": [
        14
      ],
      "name": "Massimo Cristofanilli"
    },
    {
      "affs": [
        15
      ],
      "name": "Aditya Bardia",
      "orcid": "0000-0003-4885-1157"
    },
    {
      "affs": [
        16,
        17,
        18,
        19
      ],
      "name": "Gad Getz",
      "orcid": "0000-0002-0936-0753"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c28z0a3mzp8x4.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-75976-9",
  "fulltext_url": "https://europepmc.org/articles/PMC13687546",
  "id": "c28z0a3mzp8x4",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42907427",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1306|Cancer Genomics and Diagnostics"
    ]
  ],
  "openalex": "W7213965563",
  "pdf_url": "https://europepmc.org/articles/PMC13687546?pdf=render",
  "pmcid": "PMC13687546",
  "pmid": "42907427",
  "published": "2026-09-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/c28z0a3mzp8x4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:57Z",
      "native_id": "MED:42907427",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42907427"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer Genomics and Diagnostics",
      "subfield": "oncology"
    }
  ],
  "title": "Actionable genetic landscape and dynamics in circulating DNA from 12,827 patients with metastatic breast cancer.",
  "title_text": "Actionable genetic landscape and dynamics in circulating DNA from 12,827 patients with metastatic breast cancer.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:57Z",
  "url": "https://research.draconitic.com/paper/c28z0a3mzp8x4",
  "venue": "Nature communications",
  "versions": []
}