Please use this identifier to cite or link to this item: https://doi.org/10.1186/bcr2857
Title: Mutations in the epidermal growth factor receptor (EGFR) gene in triple negative breast cancer: Possible implications for targeted therapy
Authors: Teng, Y.H.-F
Tan, W.-J
Thike, A.-A
Cheok, P.-Y
Tse, G.M.-K
Wong, N.-S
Yip, G.W.-C 
Bay, B.-H 
Tan, P.-H
Keywords: epidermal growth factor receptor
paraffin
DNA
epidermal growth factor receptor
epidermal growth factor receptor 2
estrogen receptor
progesterone receptor
adult
aged
article
breast cancer
chromosome inversion
codon
DNA extraction
exon
gene deletion
gene mutation
histopathology
human
human tissue
immunohistochemistry
major clinical study
missense mutation
mutational analysis
polymerase chain reaction
protein expression
sequence analysis
biosynthesis
breast tumor
cohort analysis
female
genetics
metabolism
middle aged
molecularly targeted therapy
mutation
nucleotide sequence
proto oncogene
Adult
Aged
Breast Neoplasms
Cohort Studies
DNA Mutational Analysis
DNA, Neoplasm
Female
Genes, erbB-1
Humans
Middle Aged
Molecular Targeted Therapy
Mutation
Receptor, Epidermal Growth Factor
Receptor, erbB-2
Receptors, Estrogen
Receptors, Progesterone
Issue Date: 2011
Citation: Teng, Y.H.-F, Tan, W.-J, Thike, A.-A, Cheok, P.-Y, Tse, G.M.-K, Wong, N.-S, Yip, G.W.-C, Bay, B.-H, Tan, P.-H (2011). Mutations in the epidermal growth factor receptor (EGFR) gene in triple negative breast cancer: Possible implications for targeted therapy. Breast Cancer Research 13 (2) : R35. ScholarBank@NUS Repository. https://doi.org/10.1186/bcr2857
Rights: Attribution 4.0 International
Abstract: Introduction: Triple negative breast cancer is associated with poorer prognosis and unresponsiveness to endocrine and anti-HER2 directed agents. Despite emerging data supporting the use of polyADP-ribose polymerase (PARP) inhibitors, complete and durable responses are rare and exploration of additional targeted therapies is needed. Epidermal growth factor receptor (EGFR) is expressed in triple negative breast cancer and several clinical trials are testing the role of anti-EGFR directed therapy. However, the rate of EGFR mutations is poorly defined. We, therefore, sought to characterize EGFR mutations in triple negative breast cancers.Methods: Seventy samples were randomly chosen from a cohort of 653 triple negative breast tumours for EGFR mutation analysis. These samples were immunostained for EGFR protein expression and consisted of negatively stained and positively stained cases. DNA was extracted from paraffin blocks and polymerase chain reaction was performed to amplify exon regions 18 to 21 of the EGFR gene. Direct sequencing of the purified PCR products was performed.Results: EGFR mutations were found in 8 of 70 samples (11.4%). Mutations were predominantly exon 19 deletions (4 of 70 samples, 5.7%), which clustered in the region spanning codons 746 to 759 within the kinase domain of EGFR. Two types of exon 19 deletions were seen: a 15 nucleotide deletion (del E746-A750) (2 of 70 samples) and a 24 nucleotide deletion (del S752 - I759) (2 of 70 samples). Other exon 19 mutations observed were the inversion of the complementary strand (1 of 70 samples). Exon 21 mutations included missense substitution, L858R (1 of 70 samples) and T847I (2 of 70 samples). Mutations observed were independent of EGFR protein expression determined by immunohistochemical staining.Conclusions: This study is among the first to document the presence and estimate the prevalence of EGFR mutations in triple negative breast cancer. These findings have potential implications for the design of clinical trials involving anti-EGFR directed therapy which currently do not select for patients based on presence of activating EGFR mutations, which may hence be underpowered to detect significant benefit in unselected populations. More complete sampling of EGFR mutation status in triple negative breast cancer is needed to determine the true mutation rate. © 2011 Teng et al.; licensee BioMed Central Ltd.
Source Title: Breast Cancer Research
URI: https://scholarbank.nus.edu.sg/handle/10635/183258
ISSN: 14655411
DOI: 10.1186/bcr2857
Rights: Attribution 4.0 International
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