Evidence map›Paper›PMID 34448090›Full record

ArticleBreast cancer research and treatment2021

Investigating the role of endogenous estrogens, hormone replacement therapy, and blockade of estrogen receptor-α activity on breast metabolic signaling.

Alana A Arnone, J Mark Cline, David R Soto-Pantoja, Katherine L Cook

Open access · hybridAbstract read
In one paragraph

Article in Breast cancer research and treatment, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.4field-weighted citation impact, top 17% 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

8 citing papers in PubMed, 10 citations in OpenAlex.

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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

4 authors at 1 institution in 1 country.

Alana A ArnoneDepartment of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC, 27157, USA.
J Mark ClineDepartment of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
David R Soto-PantojaDepartment of Surgery, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
Katherine L CookDepartment of Surgery, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA. klcook@wakehealth.edu.ORCID http://orcid.org/0000-0001-6241-0214
Wake Forest University · US

Funding

American Cancer Society RSG-16-204-01-NECAmerican Society for Radiation Oncology 637969Breast Cancer Research Foundation 637969Congressionally Directed Medical Research Programs W81XWH-20-1-0014Susan G. Komen CCR18547795
6 · The paper itself

Abstract

purposeMenopause is associated with an increased risk of estrogen receptor-positive (ER +) breast cancer. To characterize the metabolic shifts associated with reduced estrogen bioavailability on breast tissue, metabolomics was performed from ovary-intact and ovariectomized (OVX) female non-human primates (NHP). The effects of exogenous estrogen administration or estrogen receptor blockade (tamoxifen treatment) on menopause-induced metabolic changes were also investigated.

methodsBilateral ovariectomies were performed on female cynomolgus macaques (Macaca fascicularis) to model menopause. OVX NHP were then divided into untreated (n = 13), conjugated equine estrogen (CEE)-treated (n= 13), or tamoxifen-treated (n = 13) subgroups and followed for 3 years. Aged-matched ovary-intact female NHP (n = 12) were used as a premenopausal comparison group. Metabolomics was performed on snap-frozen breast tissue.

resultsChanges in several different metabolic biochemicals were noted, particularly in glucose and fatty acid metabolism. Specifically, glycolytic, Krebs cycle, acylcarnitines, and phospholipid metabolites were elevated in breast tissue from ovary-intact NHP and OVX + CEE in relation to the OVX and OVX + tamoxifen group. In contrast, treatment with CEE and tamoxifen decreased several cholesterol metabolites, compared to the ovary-intact and OVX NHP. These changes were accompanied by elevated bile acid metabolites in the ovary-intact group.

conclusionAlterations in estrogen bioavailability are associated with changes in the mammary tissue metabolome, particularly in glucose and fatty acid metabolism. Changes in these pathways may represent a bioenergetic shift in gland metabolism at menopause that may affect breast cancer risk.

Indexed as

Breast NeoplasmsEstrogensHormone Replacement TherapyAgedAnimalsEstrogen Replacement TherapyEstrogens, Conjugated (USP)FemaleHumansMacaca fascicularisOvariectomyReceptors, EstrogenEstrogensEstrogens, Conjugated (USP)Receptors, EstrogenBreast cancerConjugated equine estrogenEstrogenHormone replacement therapiesNon-targeted metabolomicsPost-menopausalTamoxifen

Identifiers

PMID34448090
PMCPMC8557185
OpenAlexW3195115132

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LicenceCC BY
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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.