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

ABSTRACT

Introduction: 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.

KEYWORDS:

• Breast cancer
• EGFR
• monoclonal antibodies (mAbs)
• tyrosine kinase inhibitors (TKIs)
• cetuximab
• panitumumab
• gefitinib
• neratinib

Article highlights

• Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer.

• Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with specific types of breast cancer, such as triple-negative, basal-like, and inflammatory breast cancer.

• Changes in tumor genomic expression status during EGFR targeted therapy can provide insights into tumor biology and drug resistance.

• The analysis of gene expression by RNA sequencing and of cytokine expression in blood samples will allow us to identify novel predictors for response.

• Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways (e.g. the inflammatory pathway) are warranted.

This box summarizes key points contained in the article.

Acknowledgments

The authors acknowledge the copyediting assistance provided by Sunita Patterson, MD Anderson Cancer Center.

Declaration of interest

N. T. Ueno has received support from Amgen regarding the provision of a drug for a clinical study (Clinicaltrial.gov ID: NCT01036087, Amgen protocol: 20159339). B. Lim has also received support from Amgen regarding the provision of a drug for a clinical study (Clinicaltrial.gov ID: NCT02593175). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported by Morgan Welch Inflammatory Breast Cancer Research Program, and State of Texas Rare and Aggressive Breast Cancer Research Program Grant, [1R01CA205043-01A1] (Ueno).