Evidence map›Paper›PMID 22042860›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2011

High levels of nuclear heat-shock factor 1 (HSF1) are associated with poor prognosis in breast cancer.

Sandro Santagata, Rong Hu, Nancy U Lin, Marc L Mendillo, Laura C Collins, Susan E Hankinson, Stuart J Schnitt, Luke Whitesell, Rulla M Tamimi, Susan Lindquist and 1 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
191citing papers in PubMed, 1 pooled it
8.8field-weighted citation impact, top 1% 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

191 citing papers in PubMed, 1 synthesis or guideline pooled it, 330 citations in OpenAlex.

  1. Pooled it
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  14. ARID1A in Gynecologic Precancers and Cancers.Reproductive sciences (Thousand Oaks, Calif.) · 2024
    Review
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131 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 6 institutions in 1 country.

Sandro SantagataDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Rong Hu
Nancy U Lin
Marc L Mendillo
Laura C Collins
Susan E Hankinson
Stuart J Schnitt
Luke Whitesell
Rulla M Tamimi
Susan Lindquist
Tan A Ince
Harvard University · USWhitehead Institute for Biomedical Research · USBrigham and Women's Hospital · USBeth Israel Deaconess Medical Center · USDana-Farber Cancer Institute · USUniversity of Miami · US

Funding

Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ROSNER, BERNARD A · 2000 to 2019
$77.8M
Variation in Receptor Tyrosine Kinases and Breast Cancer RiskP50CA089393 · NCI · DANA-FARBER CANCER INSTITUTE · PI HARRIS, LYNDSAY NORINE · 2000 to 2009
$28.8M
Epigenomic Mapping in Human Tumor Stem CellsR01CA146445 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI INCE, TAN A., LEE, TONG IHN · 2009 to 2013
$3.1M
Heat Shock Directed Drug Discovery For The Treatment Of GliomasK08NS064168 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI SANTAGATA, SANDRO · 2008 to 2012
$900k
Howard Hughes Medical InstituteNCI NIH HHS CA087969NCI NIH HHS CA089393NCI NIH HHS P01 CA087969NCI NIH HHS P50 CA089393NCI NIH HHS R01 CA146445NCI NIH HHS R01-CA146445-01NINDS NIH HHS K08 NS064168NINDS NIH HHS K08NS064168
6 · The paper itself

Abstract

Heat-shock factor 1 (HSF1) is the master transcriptional regulator of the cellular response to heat and a wide variety of other stressors. We previously reported that HSF1 promotes the survival and proliferation of malignant cells. At this time, however, the clinical and prognostic significance of HSF1 in cancer is unknown. To address this issue breast cancer samples from 1,841 participants in the Nurses' Health Study were scored for levels of nuclear HSF1. Associations of HSF1 status with clinical parameters and survival outcomes were investigated by Kaplan-Meier analysis and Cox proportional hazard models. The associations were further delineated by Kaplan-Meier analysis using publicly available mRNA expression data. Our results show that nuclear HSF1 levels were elevated in ∼80% of in situ and invasive breast carcinomas. In invasive carcinomas, HSF1 expression was associated with high histologic grade, larger tumor size, and nodal involvement at diagnosis (P < 0.0001). By using multivariate analysis to account for the effects of covariates, high HSF1 levels were found to be independently associated with increased mortality (hazards ratio: 1.62; 95% confidence interval: 1.21-2.17; P < 0.0013). This association was seen in the estrogen receptor (ER)-positive population (hazards ratio: 2.10; 95% confidence interval: 1.45-3.03; P < 0.0001). In public expression profiling data, high HSF1 mRNA levels were also associated with an increase in ER-positive breast cancer-specific mortality. We conclude that increased HSF1 is associated with reduced breast cancer survival. The findings indicate that HSF1 should be evaluated prospectively as an independent prognostic indicator in ER-positive breast cancer. HSF1 may ultimately be a useful therapeutic target in cancer.

Indexed as

Breast NeoplasmsCell NucleusFemaleHeat-Shock ProteinsHumansMiddle AgedMultivariate AnalysisPrognosisRNA, MessengerSurvival AnalysisTissue Array AnalysisHeat-Shock ProteinsRNA, Messenger

Identifiers

PMID22042860
PMCPMC3215027
OpenAlexW2121565438

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.