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Intrinsic Subtype Switching and Acquired ERBB2/HER2 Amplifications and Mutations in Breast Cancer Brain Metastases

Overview of attention for article published in JAMA Oncology, December 2016
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (82nd percentile)

Mentioned by

news
20 news outlets
blogs
1 blog
twitter
104 tweeters
facebook
7 Facebook pages
googleplus
1 Google+ user

Readers on

mendeley
13 Mendeley
Title
Intrinsic Subtype Switching and Acquired ERBB2/HER2 Amplifications and Mutations in Breast Cancer Brain Metastases
Published in
JAMA Oncology, December 2016
DOI 10.1001/jamaoncol.2016.5630
Pubmed ID
Authors

Nolan Priedigkeit, Ryan J. Hartmaier, Yijing Chen, Damir Vareslija, Ahmed Basudan, Rebecca J. Watters, Roby Thomas, Jose P. Leone, Peter C. Lucas, Rohit Bhargava, Ronald L. Hamilton, Juliann Chmielecki, Shannon L. Puhalla, Nancy E. Davidson, Steffi Oesterreich, Adam M. Brufsky, Leonie Young, Adrian V. Lee

Abstract

Patients with breast cancer (BrCa) brain metastases (BrM) have limited therapeutic options. A better understanding of molecular alterations acquired in BrM could identify clinically actionable metastatic dependencies. To determine whether there are intrinsic subtype differences between primary tumors and matched BrM and to uncover BrM-acquired alterations that are clinically actionable. In total, 20 cases of primary breast cancer tissue and resected BrM (10 estrogen receptor [ER]-negative and 10 ER-positive) from 2 academic institutions were included. Eligible cases in the discovery cohort harbored patient-matched primary breast cancer tissue and resected BrM. Given the rarity of patient-matched samples, no exclusion criteria were enacted. Two validation sequencing cohorts were used-a published data set of 17 patient-matched cases of BrM and a cohort of 7884 BrCa tumors enriched for metastatic samples. Brain metastases expression changes in 127 genes within BrCa signatures, PAM50 assignments, and ERBB2/HER2 DNA-level gains. Overall, 17 of 20 BrM retained the PAM50 subtype of the primary BrCa. Despite this concordance, 17 of 20 BrM harbored expression changes (<2-fold or >2-fold) in clinically actionable genes including gains of FGFR4 (n = 6 [30%]), FLT1 (n = 4 [20%]), AURKA (n = 2 [10%]) and loss of ESR1 expression (n = 9 [45%]). The most recurrent expression gain was ERBB2/HER2, which showed a greater than 2-fold expression increase in 7 of 20 BrM (35%). Three of these 7 cases were ERBB2/HER2-negative out of 13 ERBB2/HER2-negative in the primary BrCa cohort and became immunohistochemical positive (3+) in the paired BrM with metastasis-specific amplification of the ERBB2/HER2 locus. In an independent data set, 2 of 9 (22.2%) ERBB2/HER2-negative BrCa switched to ERBB2/HER2-positive with 1 BrM acquiring ERBB2/HER2 amplification and the other showing metastatic enrichment of the activating V777L ERBB2/HER2 mutation. An expanded cohort revealed that ERBB2/HER2 amplification and/or mutation frequency was unchanged between local disease and metastases across all sites; however, a significant enrichment was appreciated for BrM (13% local vs 24% BrM; P < .001). Breast cancer BrM commonly acquire alterations in clinically actionable genes, with metastasis-acquired ERBB2/HER2 alterations in approximately 20% of ERBB2/HER2-negative cases. These observations have immediate clinical implications for patients with ERBB2/HER2-negative breast cancer and support comprehensive profiling of metastases to inform clinical care.

Twitter Demographics

The data shown below were collected from the profiles of 104 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 31%
Lecturer 2 15%
Other 2 15%
Researcher 2 15%
Professor > Associate Professor 2 15%
Other 1 8%
Readers by discipline Count As %
Agricultural and Biological Sciences 5 38%
Medicine and Dentistry 5 38%
Biochemistry, Genetics and Molecular Biology 1 8%
Business, Management and Accounting 1 8%
Engineering 1 8%
Other 0 0%

Attention Score in Context

This research output has an Altmetric Attention Score of 223. 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 05 June 2017.
All research outputs
#30,514
of 8,364,610 outputs
Outputs from JAMA Oncology
#83
of 996 outputs
Outputs of similar age
#2,511
of 278,949 outputs
Outputs of similar age from JAMA Oncology
#17
of 99 outputs
Altmetric has tracked 8,364,610 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 996 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 83.9. This one has done particularly well, scoring higher than 91% 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 278,949 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 99 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.