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Patient survival and tumor characteristics associated with CHEK2:p.I157T – findings from the Breast Cancer Association Consortium

Overview of attention for article published in Breast Cancer Research, October 2016
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Citations

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Title
Patient survival and tumor characteristics associated with CHEK2:p.I157T – findings from the Breast Cancer Association Consortium
Published in
Breast Cancer Research, October 2016
DOI 10.1186/s13058-016-0758-5
Pubmed ID
Authors

Taru A. Muranen, Carl Blomqvist, Thilo Dörk, Anna Jakubowska, Päivi Heikkilä, Rainer Fagerholm, Dario Greco, Kristiina Aittomäki, Stig E. Bojesen, Mitul Shah, Alison M. Dunning, Valerie Rhenius, Per Hall, Kamila Czene, Judith S. Brand, Hatef Darabi, Jenny Chang-Claude, Anja Rudolph, Børge G. Nordestgaard, Fergus J. Couch, Steven N. Hart, Jonine Figueroa, Montserrat García-Closas, Peter A. Fasching, Matthias W. Beckmann, Jingmei Li, Jianjun Liu, Irene L. Andrulis, Robert Winqvist, Katri Pylkäs, Arto Mannermaa, Vesa Kataja, Annika Lindblom, Sara Margolin, Jan Lubinski, Natalia Dubrowinskaja, Manjeet K. Bolla, Joe Dennis, Kyriaki Michailidou, Qin Wang, Douglas F. Easton, Paul D. P. Pharoah, Marjanka K. Schmidt, Heli Nevanlinna

Abstract

P.I157T is a CHEK2 missense mutation associated with a modest increase in breast cancer risk. Previously, another CHEK2 mutation, the protein truncating c.1100delC has been associated with poor prognosis of breast cancer patients. Here, we have investigated patient survival and characteristics of breast tumors of germ line p.I157T carriers. We included in the analyses 26,801 European female breast cancer patients from 15 studies participating in the Breast Cancer Association Consortium. We analyzed the association between p.I157T and the clinico-pathological breast cancer characteristics by comparing the p.I157T carrier tumors to non-carrier and c.1100delC carrier tumors. Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models. Additionally, we explored the p.I157T-associated genomic gene expression profile using data from breast tumors of 183 Finnish female breast cancer patients (ten p.I157T carriers) (GEO: GSE24450). Differential gene expression analysis was performed using a moderated t test. Functional enrichment was investigated using the DAVID functional annotation tool and gene set enrichment analysis (GSEA). The tumors were classified into molecular subtypes according to the St Gallen 2013 criteria and the PAM50 gene expression signature. P.I157T was not associated with increased risk of early death, breast cancer-associated death or distant metastasis relapse, and there was a significant difference in prognosis associated with the two CHEK2 mutations, p.I157T and c.1100delC. Furthermore, p.I157T was associated with lobular histological type and clinico-pathological markers of good prognosis, such as ER and PR expression, low TP53 expression and low grade. Gene expression analysis suggested luminal A to be the most common subtype for p.I157T carriers and CDH1 (cadherin 1) target genes to be significantly enriched among genes, whose expression differed between p.I157T and non-carrier tumors. Our analyses suggest that there are fundamental differences in breast tumors of CHEK2:p.I157T and c.1100delC carriers. The poor prognosis associated with c.1100delC cannot be generalized to other CHEK2 mutations.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Finland 1 3%
Unknown 31 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 19%
Researcher 5 16%
Professor 5 16%
Student > Postgraduate 4 13%
Student > Bachelor 4 13%
Other 4 13%
Unknown 4 13%
Readers by discipline Count As %
Medicine and Dentistry 15 47%
Biochemistry, Genetics and Molecular Biology 5 16%
Agricultural and Biological Sciences 2 6%
Nursing and Health Professions 1 3%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Other 3 9%
Unknown 5 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 14 October 2016.
All research outputs
#6,155,031
of 8,515,357 outputs
Outputs from Breast Cancer Research
#779
of 1,054 outputs
Outputs of similar age
#163,254
of 253,463 outputs
Outputs of similar age from Breast Cancer Research
#17
of 27 outputs
Altmetric has tracked 8,515,357 research outputs across all sources so far. This one is in the 24th percentile – i.e., 24% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,054 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.2. This one is in the 22nd percentile – i.e., 22% of its peers scored the same or lower than it.
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 253,463 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 27 others from the same source and published within six weeks on either side of this one. This one is in the 29th percentile – i.e., 29% of its contemporaries scored the same or lower than it.