Perspectives on Epidermal Growth Factor Receptor Regulation in Triple-Negative Breast Cancer: Ligand-Mediated Mechanisms of Receptor Regulation and Potential for Clinical Targeting

Currently, there are no effective targeted therapies for triple-negative breast cancer (TNBC) indicating a critical unmet need for breast cancer patients. Tumors that fall into the triple-negative category of breast cancers do not respond to the targeted therapies currently approved for breast cancer treatment, such as endocrine therapy (tamoxifen, aromatase inhibitors) or human epidermal growth factor receptor-2 (HER2) inhibitors (trastuzumab, lapatinib), because these tumors lack the most common breast cancer markers: estrogen receptor, progesterone receptor, and HER2. While many patients with TNBC respond to chemotherapy, subsets of patients fare poorly and relapse very quickly. Studies indicate that epidermal growth factor receptor (EGFR) is frequently overrepresented in TNBC (>50%), suggesting EGFR could be used as a biomarker and target in breast cancer. While it is clear that this growth factor receptor plays an integral role in TNBC, little is known about the mechanisms of sustained EGFR activation and how to target this protein despite availability of EGFR-targeted inhibitors, suggesting that our understanding of EGFR deregulation in TNBC is incomplete.