Evidence map›Paper›PMID 39368973›Full record

ArticleNPJ breast cancer2024

Clinical and immune responses to neoadjuvant fulvestrant with or without enzalutamide in ER+/Her2- breast cancer.

Anthony D Elias, Alyse W Staley, Monica Fornier, Gregory A Vidal, Vida Alami, Sharon Sams, Nicole S Spoelstra, Andrew Goodspeed, Peter Kabos, Jennifer R Diamond and 11 more

Registry-linked trialAbstract read
In one paragraph

Article in NPJ breast cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02955394 (Randomized Phase II Trial of Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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.

NCT02955394 phase2active not recruitingnot on this map

Randomized Phase II Trial of Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer

TypeinterventionalSponsorUniversity of Colorado, DenverRan2017 to 2027Enrolled61ConditionsBreast CancerArmsEnzalutamide, Fulvestrant
3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
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

21 authors.

Anthony D EliasDepartment of Medicine/Medical Oncology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.ORCID http://orcid.org/0000-0002-6509-9211
Alyse W StaleyDepartment of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.ORCID http://orcid.org/0000-0001-8938-5063
Monica FornierDepartment of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.ORCID http://orcid.org/0000-0003-3326-5972
Gregory A VidalWest Cancer Center and Research Institute and Department of Medicine, University of Tennessee Health Sciences Center, Tennessee, USA.
Vida AlamiUniversity of Colorado Cancer Center, Biostatistics and Bioinformatics Shared Resource, Aurora, Colorado, USA.
Sharon SamsDepartment of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Nicole S SpoelstraDepartment of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Andrew GoodspeedUniversity of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Peter KabosDepartment of Medicine/Medical Oncology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Jennifer R DiamondDepartment of Medicine/Medical Oncology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Elena ShagisultanovaDepartment of Medicine/Medical Oncology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.ORCID http://orcid.org/0000-0003-1389-1116
Rosa I GallagherCenter for Applied Proteomics and Molecular Medicine, George Mason University, Fairfax, Virginia, USA.ORCID http://orcid.org/0000-0003-3887-8399
Julia D WulfkuhleCenter for Applied Proteomics and Molecular Medicine, George Mason University, Fairfax, Virginia, USA.
Emanuel F PetricoinCenter for Applied Proteomics and Molecular Medicine, George Mason University, Fairfax, Virginia, USA.
Kathryn L ZolmanDepartment of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Tessa McSpaddenUniversity of Colorado Cancer Center, Oncology Clinical Research Support Team, Aurora, Colorado, USA.
Kimberly R JordanDepartment of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Jill E SlanskyDepartment of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.ORCID http://orcid.org/0000-0003-3820-1724
Virginia F BorgesDepartment of Medicine/Medical Oncology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.ORCID http://orcid.org/0000-0003-1158-7524
Dexiang GaoDepartment of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Jennifer K RicherDepartment of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA. jennifer.richer@cuanschutz.edu.ORCID http://orcid.org/0000-0002-9960-0991

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Michael Jason de la Cruz · 1985 to 2026
$347.4M
University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA046934U.S. Department of Defense (United States Department of Defense) BCRP BC120183 W81XWH-13-1-0090/91
6 · The paper itself

Abstract

Most ER+ breast cancers (BC) express androgen receptors (AR). This randomized phase II trial of 4 months of neoadjuvant fulvestrant (Fulv) alone or with enzalutamide (Combo) assessed whether adding AR blockade to Fulv would limit residual tumor at the time of surgery, as measured by modified preoperative endocrine predictive index (PEPI) score. Eligible patients were women with ER+/HER2- primary BC cT2 or greater. Stratification factors were clinical node and T-stage. Fresh tumor biopsies were required at study entry, after 4 weeks on therapy (W5), and at surgery. Laboratory analyses on tumors included immunochemistry (IHC) for ER/PR/AR/GR and Ki67 protein, evaluation of gene expression, multiplex for myeloid lineage immune cells, reverse-phase protein array, and plasma metabolomic analyses. Of 69 consented patients, 59 were evaluable. Toxicity was as expected with endocrine therapy. Combo achieved PEPI = 0 more frequently (24%: 8/33) than Fulv (8%: 2/26). Ki67 was ≤10% across arms by W5 in 76% of tumors. Activation of mTOR pathway proteins was elevated in tumors with poor Ki67 response. Tumors in both arms showed decreased estrogen-regulated and cell division gene sets, while Combo arm tumors uniquely exhibited enrichment of immune activation gene sets, including interferon gamma, complement, inflammation, antigen processing, and B and T cell activation. Multiplex IHC showed significantly reduced tumor-associated macrophages and CD14+/HLADR-/CD68- MDSCs in Combo tumors at W5. In summary, Combo tumors showed a higher PEPI = 0 response, Ki67 response, and more activated tumor immune microenvironment than Fulv. The odds of response were 4.6-fold higher for patients with ILC versus IDC. (Trial registration: This trial is registered at Clinicaltrials.gov ( https://www.clinicaltrials.gov/study/NCT02955394?id=16-1042&rank=1 ). The trial registration number is NCT02955394. The full trial protocol is available under Study Details at the Clinicaltrials.gov link provided).

Identifiers

PMID39368973
PMCPMC11455938

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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 Socratic graph.