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S6 kinase signaling: tamoxifen response and prognostic indication in two breast cancer cohorts

Overview of attention for article published in Endocrine-Related Cancer, June 2015
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  • Good Attention Score compared to outputs of the same age (67th percentile)
  • Good Attention Score compared to outputs of the same age and source (71st percentile)

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Title
S6 kinase signaling: tamoxifen response and prognostic indication in two breast cancer cohorts
Published in
Endocrine-Related Cancer, June 2015
DOI 10.1530/erc-14-0513
Pubmed ID
Authors

Josefine Bostner, Elin Karlsson, Cecilia Bivik Eding, Gizeh Perez-Tenorio, Hanna Franzén, Aelita Konstantinell, Tommy Fornander, Bo Nordenskjöld, Olle Stål

Abstract

Detection of signals in the mammalian target of rapamycin (mTOR) and the estrogen receptor (ER) pathways may be a future clinical tool for the prediction of adjuvant treatment response in primary breast cancer. Using immunohistological staining, we investigated the value of the mTOR targets p70-S6 kinase (S6K) 1 and 2 as biomarkers for tamoxifen benefit in two independent clinical trials comparing adjuvant tamoxifen with no tamoxifen or 5 years versus 2 years of tamoxifen treatment. In addition, the prognostic value of the S6Ks was evaluated. We found that S6K1 correlated with proliferation, HER2 status, and cytoplasmic AKT activity, whereas high protein expression levels of S6K2 and phosphorylated (p) S6K were more common in ER-positive, and low-proliferative tumors with pAKT-s473 localized to the nucelus. Nuclear accumulation of S6K1 was indicative of a reduced tamoxifen effect (hazard ratio (HR): 1.07, 95% CI: 0.53-2.81, P=0.84), compared with a significant benefit from tamoxifen treatment in patients without tumor S6K1 nuclear accumulation (HR: 0.42, 95% CI: 0.29-0.62, P<0.00001). Also S6K1 and S6K2 activation, indicated by pS6K-t389 expression, was associated with low benefit from tamoxifen (HR: 0.97, 95% CI: 0.50-1.87, P=0.92). In addition, high protein expression of S6K1, independent of localization, predicted worse prognosis in a multivariate analysis, P=0.00041 (cytoplasm), P=0.016 (nucleus). In conclusion, the mTOR-activated kinases S6K1 and S6K2 interfere with proliferation and response to tamoxifen. Monitoring their activity and intracellular localization may provide biomarkers for breast cancer treatment, allowing the identification of a group of patients less likely to benefit from tamoxifen and thus in need of an alternative or additional targeted treatment.

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The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 37 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 14%
Student > Master 5 14%
Student > Bachelor 4 11%
Other 4 11%
Professor > Associate Professor 4 11%
Other 8 22%
Unknown 7 19%
Readers by discipline Count As %
Medicine and Dentistry 10 27%
Biochemistry, Genetics and Molecular Biology 7 19%
Agricultural and Biological Sciences 6 16%
Pharmacology, Toxicology and Pharmaceutical Science 2 5%
Chemical Engineering 1 3%
Other 3 8%
Unknown 8 22%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 April 2016.
All research outputs
#8,185,927
of 25,373,627 outputs
Outputs from Endocrine-Related Cancer
#497
of 1,509 outputs
Outputs of similar age
#91,808
of 281,402 outputs
Outputs of similar age from Endocrine-Related Cancer
#9
of 32 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 1,509 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one has gotten more attention than average, scoring higher than 66% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 281,402 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 67% of its contemporaries.
We're also able to compare this research output to 32 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.