Evidence map›Paper›PMID 34930399›Full record

ArticleBreast cancer research : BCR2021

Low thyroid hormone receptor alpha-2 (THRα-2) tumor expression is associated with unfavorable tumor characteristics and high breast cancer mortality.

Malte Sandsveden, Signe Borgquist, Ann H Rosendahl, Jonas Manjer

Open access · goldAbstract read
PubMed Full text at PMC Publisher
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 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 22% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Review
  6. TRα2-An Untuned Second Fiddle or Fine-Tuning Thyroid Hormone Action?International journal of molecular sciences · 2022
    Review
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 3 institutions in 2 countries.

Malte SandsvedenDepartment of Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden. malte.sandsveden@med.lu.se.ORCID 0000-0002-4630-5075
Signe BorgquistDepartment of Oncology, Aarhus University Hospital, Aarhus University, Aarhus, Denmark.
Ann H Rosendahl *Department of Clinical Sciences Lund, Oncology, Lund University, Skåne University Hospital, Lund, Sweden.
Jonas Manjer *Department of Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
Lund University · SEAarhus University Hospital · DKMalmö University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe active thyroid hormone triiodothyronine (T3) has been found to have an estrogen-like effect on breast cancer cells. Thyroid hormone receptor alpha-2 (THRα-2) acts as an antagonist for triiodothyronine (T3) signaling, and a low expression has been associated with unfavorable tumor characteristics and a higher mortality in breast cancer. However, the evidence are not conclusive. The present study evaluates tumor-specific THRα-2 expression in invasive breast cancers and its association with tumor characteristics and long-term mortality in a large population.

methodThe Malmö Diet and Cancer Study (MDCS), a population-based cohort in Sweden that included 17,035 women from 1991 to 1996, was used. Women diagnosed with breast cancer during 1991-2010 were eligible for inclusion. A tissue micro array was constructed from stored tumor material and stained for THRα-2 using immunohistochemistry. Tumors from 654 patients were scored regarding the intensity and the fraction of cells stained, then dichotomized into low or high expression. Date and cause of death were collected up until 2018-12-31. Tumor- and patient characteristics were available from the MDCS. Missing data was imputed using chained equations. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for low vs high expression of THRα-2 related to specific tumor factors. Mortality was evaluated with Kaplan-Meier curves and Cox regression, rendering hazard ratios (HRs). Analyses were also stratified for estrogen receptor (ER) status.

resultsWe found strong evidence of an association between low THRα-2 and unfavorable tumor characteristics, including estrogen receptor negativity: OR 4.04 (95% CI 2.28-7.15) and tumor size > 20-50 mm: OR 2.20 (95% CI 1.39-3.49). We found evidence of increased breast cancer-specific mortality for women with low THRα-2, HR 1.38 (95% CI 0.96-1.99), which remained after adjusting for age at diagnosis, HR 1.48 (95% CI 1.03-2.14), but not after adjusting for relevant prognostic factors, HR 0.98 (95% CI 0.66-1.45). THRα-2 expression in ER-negative tumors had an inverse correlation with overall mortality, HR 0.27 (95% CI 0.11-0.65).

conclusionLow tumor-specific THRα-2 expression was in this study associated with prognostically unfavorable tumor characteristics and a higher mortality in breast cancer, but not independent from other prognostic factors.

Indexed as

Breast NeoplasmsThyroid Hormone Receptors alphaBreastFemaleHumansPrognosisProportional Hazards ModelsTriiodothyronineThyroid Hormone Receptors alphaTriiodothyronineBreast cancerMortalityThyroid hormone receptorTumor characteristics

Identifiers

PMID34930399
PMCPMC8691018
OpenAlexW4200408805

What OpenQuestion holds

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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.