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Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer.

ABSTRACT: Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered: This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion: Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted.

SUBMITTER: Matsuda N

PROVIDER: S-EPMC5826640 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer.

Matsuda Naoko N Lim Bora B Wang Xiaoping X Ueno Naoto T NT

Expert opinion on investigational drugs 20170308 4

<h4>Introduction</h4>Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered: This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion: Recent studies ha ...[more]

PMID: 28271910

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Project description: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.

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Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer.

Publications

Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer.

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