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The BRCA1ness signature is associated significantly with response to PARP inhibitor treatment versus control in the I-SPY 2 randomized neoadjuvant setting

Overview of attention for article published in Breast Cancer Research, August 2017
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Title
The BRCA1ness signature is associated significantly with response to PARP inhibitor treatment versus control in the I-SPY 2 randomized neoadjuvant setting
Published in
Breast Cancer Research, August 2017
DOI 10.1186/s13058-017-0861-2
Pubmed ID
Authors

Tesa M. Severson, Denise M. Wolf, Christina Yau, Justine Peeters, Diederik Wehkam, Philip C. Schouten, Suet-Feung Chin, Ian J. Majewski, Magali Michaut, Astrid Bosma, Bernard Pereira, Tycho Bismeijer, Lodewyk Wessels, Carlos Caldas, René Bernards, Iris M. Simon, Annuska M. Glas, Sabine Linn, Laura van ‘t Veer

Abstract

Patients with BRCA1-like tumors correlate with improved response to DNA double-strand break-inducing therapy. A gene expression-based classifier was developed to distinguish between BRCA1-like and non-BRCA1-like tumors. We hypothesized that these tumors may also be more sensitive to PARP inhibitors than standard treatments. A diagnostic gene expression signature (BRCA1ness) was developed using a centroid model with 128 triple-negative breast cancer samples from the EU FP7 RATHER project. This BRCA1ness signature was then tested in HER2-negative patients (n = 116) from the I-SPY 2 TRIAL who received an oral PARP inhibitor veliparib in combination with carboplatin (V-C), or standard chemotherapy alone. We assessed the association between BRCA1ness and pathologic complete response in the V-C and control arms alone using Fisher's exact test, and the relative performance between arms (biomarker × treatment interaction, likelihood ratio p < 0.05) using a logistic model and adjusting for hormone receptor status (HR). We developed a gene expression signature to identify BRCA1-like status. In the I-SPY 2 neoadjuvant setting the BRCA1ness signature associated significantly with response to V-C (p = 0.03), but not in the control arm (p = 0.45). We identified a significant interaction between BRCA1ness and V-C (p = 0.023) after correcting for HR. A genomic-based BRCA1-like signature was successfully translated to an expression-based signature (BRC1Aness). In the I-SPY 2 neoadjuvant setting, we determined that the BRCA1ness signature is capable of predicting benefit of V-C added to standard chemotherapy compared to standard chemotherapy alone. I-SPY 2 TRIAL beginning December 31, 2009: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer (I-SPY 2), NCT01042379 .

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter 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 67 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 67 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 15 22%
Other 12 18%
Student > Ph. D. Student 10 15%
Student > Master 6 9%
Student > Bachelor 4 6%
Other 8 12%
Unknown 12 18%
Readers by discipline Count As %
Medicine and Dentistry 24 36%
Biochemistry, Genetics and Molecular Biology 13 19%
Agricultural and Biological Sciences 8 12%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Psychology 2 3%
Other 5 7%
Unknown 13 19%

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 12 May 2018.
All research outputs
#10,314,703
of 12,926,183 outputs
Outputs from Breast Cancer Research
#1,196
of 1,462 outputs
Outputs of similar age
#195,993
of 266,059 outputs
Outputs of similar age from Breast Cancer Research
#10
of 16 outputs
Altmetric has tracked 12,926,183 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,462 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.0. This one is in the 8th percentile – i.e., 8% 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 266,059 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 16 others from the same source and published within six weeks on either side of this one. This one is in the 6th percentile – i.e., 6% of its contemporaries scored the same or lower than it.