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Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer

Overview of attention for article published in Breast Cancer Research, June 2018
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Title
Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer
Published in
Breast Cancer Research, June 2018
DOI 10.1186/s13058-018-0989-8
Pubmed ID
Authors

Nadine Norton, Nicholas Fox, Christie-Ann McCarl, Kathleen S. Tenner, Karla Ballman, Courtney L. Erskine, Brian M. Necela, Donald Northfelt, Winston W. Tan, Carmen Calfa, Mark Pegram, Gerardo Colon-Otero, Edith A. Perez, Raphael Clynes, Keith L. Knutson

Abstract

Resected HER2 breast cancer patients treated with adjuvant trastuzumab and chemotherapy have superior survival compared to patients treated with chemotherapy alone. We previously showed that trastuzumab and chemotherapy induce HER2-specific antibodies which correlate with improved survival in HER2 metastatic breast cancer patients. It remains unclear whether the generation of immunity required trastuzumab and whether endogenous antibody immunity is associated with improved disease-free survival in the adjuvant setting. In this study, we addressed this question by analyzing serum anti-HER2 antibodies from a subset of patients enrolled in the NCCTG trial N9831, which includes an arm (Arm A) in which trastuzumab was not used. Arms B and C received trastuzumab sequentially or concurrently to chemotherapy, respectively. Pre-and post-treatment initiation sera were obtained from 50 women enrolled in N9831. Lambda IgG antibodies (to avoid detection of trastuzumab) to HER2 were measured and compared between arms and with disease-free survival. Prior to therapy, across all three arms, N9831 patients had similar mean anti-HER2 IgG levels. Following treatment, the mean levels of antibodies increased in the trastuzumab arms but not the chemotherapy-only arm. The proportion of patients who demonstrated antibodies increased by 4% in Arm A and by 43% in the Arms B and C combined (p = 0.003). Cox modeling demonstrated that larger increases in antibodies were associated with improved disease-free survival in all patients (HR = 0.23; p = 0.04). These results show that the increased endogenous antibody immunity observed in adjuvant patients treated with combination trastuzumab and chemotherapy is clinically significant, in view of its correlation with improved disease-free survival. The findings may have important implications for predicting treatment outcomes in patients treated with trastuzumab in the adjuvant setting. ClinicalTrials.gov, NCT00005970 . Registered on July 5, 2000.

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The data shown below were collected from the profiles of 2 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 57 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 57 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 9 16%
Student > Ph. D. Student 7 12%
Researcher 5 9%
Student > Master 5 9%
Professor 3 5%
Other 11 19%
Unknown 17 30%
Readers by discipline Count As %
Medicine and Dentistry 11 19%
Pharmacology, Toxicology and Pharmaceutical Science 6 11%
Biochemistry, Genetics and Molecular Biology 4 7%
Nursing and Health Professions 3 5%
Immunology and Microbiology 2 4%
Other 8 14%
Unknown 23 40%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 10 May 2019.
All research outputs
#16,728,456
of 25,382,440 outputs
Outputs from Breast Cancer Research
#1,481
of 2,054 outputs
Outputs of similar age
#209,777
of 341,958 outputs
Outputs of similar age from Breast Cancer Research
#26
of 37 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,054 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.2. This one is in the 25th percentile – i.e., 25% 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 341,958 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 37 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.