Evidence map›Paper›PMID 34717714›Full record

ArticleBreast cancer research : BCR2021

An immune-humanized patient-derived xenograft model of estrogen-independent, hormone receptor positive metastatic breast cancer.

Sandra D Scherer, Alessandra I Riggio, Fadi Haroun, Yoko S DeRose, H Atakan Ekiz, Maihi Fujita, Jennifer Toner, Ling Zhao, Zheqi Li, Steffi Oesterreich and 2 more

Open access · goldAbstract read
In one paragraph

Article in Breast cancer research : BCR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.4field-weighted citation impact, top 8% of its field
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

29 citing papers in PubMed, 37 citations in OpenAlex.

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  14. Rat Models of Hormone Receptor-Positive Breast Cancer.Journal of mammary gland biology and neoplasia · 2024
    Review
  15. The Power and Promise of Patient-Derived Xenografts of Human Breast Cancer.Cold Spring Harbor perspectives in medicine · 2024
    Review
  16. Breast Cancer Immunity: It is TIME for the Next Chapter.Cold Spring Harbor perspectives in medicine · 2024
    Review
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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

12 authors at 2 institutions in 1 country.

Sandra D SchererDepartment of Oncological Sciences, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
Alessandra I RiggioDepartment of Oncological Sciences, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
Fadi HarounDepartment of Oncological Sciences, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
Yoko S DeRoseDepartment of Oncological Sciences, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
H Atakan EkizDepartment of Oncological Sciences, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
Maihi FujitaDepartment of Oncological Sciences, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
Jennifer TonerDepartment of Oncological Sciences, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
Ling ZhaoDepartment of Oncological Sciences, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
Zheqi LiDepartment of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, Magee Women's Research Institute, University of Pittsburgh, 204 Craft Avenue, Pittsburgh, PA, 15213, USA.
Steffi OesterreichDepartment of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, Magee Women's Research Institute, University of Pittsburgh, 204 Craft Avenue, Pittsburgh, PA, 15213, USA.
Ahmed A SamatarZentalis Pharmaceuticals, Inc., 10835 Road to the Cure, Suite 205, San Diego, CA, 92121, USA.
Alana L WelmDepartment of Oncological Sciences, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA. alana.welm@hci.utah.edu.ORCID 0000-0002-1412-1351
University of Utah · USUniversity of Pittsburgh · US

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jared P Rutter · 1986 to 2026
$72.6M
Utah Center for Clinical and Translational ScienceUL1TR002538 · NCATS · UNIVERSITY OF UTAH · PI HESS, RACHEL, MAJERSIK, JENNIFER JUHL · 2018 to 2022
$26.0M
Mechanism-based strategies to target ER-mutant endocrine resistant breast cancerR01CA221303 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI OESTERREICH, STEFFI · 2018 to 2022
$2.0M
NCATS NIH HHS UL1 TR002538NCI NIH HHS 5P30CA042014NCI NIH HHS P30 CA042014NCI NIH HHS R01 CA221303NIH HHS UL1TR002538
6 · The paper itself

Abstract

backgroundMetastatic breast cancer (MBC) is incurable, with a 5-year survival rate of 28%. In the USA, more than 42,000 patients die from MBC every year. The most common type of breast cancer is estrogen receptor-positive (ER+), and more patients die from ER+ breast cancer than from any other subtype. ER+ tumors can be successfully treated with hormone therapy, but many tumors acquire endocrine resistance, at which point treatment options are limited. There is an urgent need for model systems that better represent human ER+ MBC in vivo, where tumors can metastasize. Patient-derived xenografts (PDX) made from MBC spontaneously metastasize, but the immunodeficient host is a caveat, given the known role of the immune system in tumor progression and response to therapy. Thus, we attempted to develop an immune-humanized PDX model of ER+ MBC.

methodsNSG-SGM3 mice were immune-humanized with CD34+ hematopoietic stem cells, followed by engraftment of human ER+ endocrine resistant MBC tumor fragments. Strategies for exogenous estrogen supplementation were compared, and immune-humanization in blood, bone marrow, spleen, and tumors was assessed by flow cytometry and tissue immunostaining. Characterization of the new model includes assessment of the human tumor microenvironment performed by immunostaining.

resultsWe describe the development of an immune-humanized PDX model of estrogen-independent endocrine resistant ER+ MBC. Importantly, our model harbors a naturally occurring ESR1 mutation, and immune-humanization recapitulates the lymphocyte-excluded and myeloid-rich tumor microenvironment of human ER+ breast tumors.

conclusionThis model sets the stage for development of other clinically relevant models of human breast cancer and should allow future studies on mechanisms of endocrine resistance and tumor-immune interactions in an immune-humanized in vivo setting.

Indexed as

Drug Resistance, NeoplasmAnimalsAntigens, CD34Breast NeoplasmsDisease Models, AnimalEstrogen Receptor alphaEstrogensFemaleHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHeterograftsHumansMiceMice, Inbred NODMice, SCIDMice, TransgenicAntigens, CD34ESR1 protein, humanEstrogen Receptor alphaEstrogensReceptors, EstrogenBreast cancer tumor microenvironmentEndocrine resistance modelER+ metastatic breast cancerER+ PDXESR1 mutationEstrogen supplementationHumanized PDXImmune-humanizationY537S

Identifiers

PMID34717714
PMCPMC8556932
OpenAlexW3209623819

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.