Type

Journal Article

Authors

Alex J Eustace
Bryan T Hennessy
William M Gallagher
John Crown
Susan Kennedy
Elaine W Kay
Joanna Fay
Aoife Carr
Naomi Elster
Malgorzata Milewska
and 8 others

Subjects

Medicine & Nursing

Topics
breast cancer kaplan meier next generation sequencing clinical assessment cancer survival regression analysis her2 positive single nucleotide polymorphisms

The impact of ERBB-family germline single nucleotide polymorphisms on survival response to adjuvant trastuzumab treatment in HER2-positive breast cancer. (2016)

Abstract Trastuzumab treatment for women with HER2-positive breast cancer (BC) resulted in the significant improvement of both relapse free survival (RFS) and overall survival (OS). However, many women who are classified as HER2-positive do not respond. Many studies have focused on the role of somatic mutations rather than germline polymorphisms in trastuzumab resistance. We completed an Agena MassArray screen of 10 ERBB-family single nucleotide polymorphisms (SNPs) in 194 adjuvant trastuzumab treated HER2-positive BC patients. SNPs in EGFR genes have a significant association with RFS and OS. Patients with the minor allele of EGFR N158N had significantly worse OS (hazard ratio (HR) = 4.01, (confidence interval (CI) = 1.53- 10.69), p = 0.05) relative to those with either the heterozygous or wild-type (WT) allele. Patients with the minor allele of EGFR T903T (HR = 3.52, (CI = 1.38- 8.97), p = 0.05) had worse RFS relative to those with either the heterozygous or WT allele. Using next generation sequencing (NGS) we identified ERBB-family (EGFR, HER2, HER3 and HER4) single nucleotide polymorphisms (SNPs) that occurred in 2 or more patients of a 32 HER2-positive BC patient cohort. Agena MassArray analysis confirmed the frequency of these SNPs in 194 women with HER2-positive BC who received trastuzumab in the adjuvant setting. Using Kaplan-Meier estimates and Cox regression analysis we correlated the presence of ERBB-family SNPs with both RFS and OS. The presence of germline ERBB-family SNPs may play an important role in how a patient responds to adjuvant trastuzumab, and clinical assessment of these SNPs by targeted genetic screening of patients' blood may be important to stratify patients for treatment.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Alex J Eustace, Bryan T Hennessy, William M Gallagher, John Crown, Susan Kennedy, Elaine W Kay, Joanna Fay, Aoife Carr, Naomi Elster, Malgorzata Milewska and 8 others

Experts in our system

1
Alex J Eustace
Dublin City University
 
2
Bryan T Hennessy
Royal College of Surgeons in Ireland
Total Publications: 33
 
3
William M Gallagher
University College Dublin
Total Publications: 148
 
4
John Crown
Dublin City University
Total Publications: 104
 
5
Susan Kennedy
Dublin City University
Total Publications: 40
 
6
Elaine W Kay
Royal College of Surgeons in Ireland
Total Publications: 157
 
7
Joanna Fay
Royal College of Surgeons in Ireland
Total Publications: 24
 
8
Aoife Carr
Royal College of Surgeons in Ireland
Total Publications: 8
 
9
N Elster
Royal College of Surgeons in Ireland
Total Publications: 4
 
10
Malgorzata Milewska
Royal College of Surgeons in Ireland
Total Publications: 13