Evidence map›Paper›PMID 42907427›Full record

ArticleNature communications2026

Actionable genetic landscape and dynamics in circulating DNA from 12,827 patients with metastatic breast cancer.

Ignaty Leshchiner, Arielle J Medford, Justin Cha, Lesli A Kiedrowski, Andrzej Niemierko, Jennifer C Keenan, Charles S Dai, Laura M Spring, Beverly Moy, Seth A Wander and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Ignaty Leshchiner *Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-8942-9265
Arielle J Medford *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Justin Cha *Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-6026-2211
Lesli A KiedrowskiGuardant Health, Palo Alto, CA, USA.ORCID 0000-0001-5081-2005
Andrzej NiemierkoKrantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Jennifer C KeenanKrantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Charles S DaiHarvard Medical School, Boston, MA, USA.
Laura M SpringHarvard Medical School, Boston, MA, USA.ORCID 0000-0001-8904-3514
Beverly MoyHarvard Medical School, Boston, MA, USA.ORCID 0000-0003-3472-1140
Seth A WanderHarvard Medical School, Boston, MA, USA.
Neelima VidulaHarvard Medical School, Boston, MA, USA.
Steven J IsakoffHarvard Medical School, Boston, MA, USA.ORCID 0000-0002-6677-1014
Dejan JuricHarvard Medical School, Boston, MA, USA.ORCID 0000-0003-2983-7704
Mendy MillerBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Andrew A DavisWashington University in St Louis, St Louis, MO, USA.
Lorenzo GerratanaDepartment of Medicine, University of Udine, Udine, Italy.
Ami ShahNorthwestern University, Chicago, IL, USA.
Ben H ParkVanderbilt-Ingram Cancer Center, Nashville, TN, USA.ORCID 0000-0001-8119-2291
Adam BrufskyUniversity of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0001-8080-7960
Joyce O'ShaughnessyBaylor University Medical Center, Texas Oncology, Dallas, TX, USA.
Rebecca J NagyGuardant Health, Palo Alto, CA, USA.
Leif W EllisenHarvard Medical School, Boston, MA, USA.ORCID 0000-0003-0444-7910
Massimo CristofanilliWeill Cornell Medicine, New York, NY, USA.
Aditya BardiaUCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA. ABardia@mednet.ucla.edu.ORCID 0000-0003-4885-1157
Gad GetzBroad Institute of MIT and Harvard, Cambridge, MA, USA. gadgetz@broadinstitute.org.ORCID 0000-0002-0936-0753

Funding

Dana Farber/Harvard Cancer Consortium Career Development Program in Clinical OncologyK12CA087723 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Tsai Ting · 2002 to 2026
$17.9M
NCI NIH HHS K12 CA087723
6 · The paper itself

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.

Indexed as

Breast NeoplasmsCell-Free Nucleic AcidsCirculating Tumor DNABiomarkers, TumorClass I Phosphatidylinositol 3-KinasesDrug Resistance, NeoplasmEstrogen Receptor alphaFemaleHigh-Throughput Nucleotide SequencingHumansMutationNeoplasm MetastasisProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseAKT1 protein, humanBiomarkers, TumorCell-Free Nucleic AcidsCirculating Tumor DNAClass I Phosphatidylinositol 3-KinasesESR1 protein, humanEstrogen Receptor alphaPIK3CA protein, humanProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePTEN protein, human

Identifiers

PMID42907427
PMCPMC13687546

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.