New Insights to Reshape the Management of Patients with Metastatic Breast Cancer - Focus on Overcoming Challenges in HER2 Status Interpretation

Abstract

Approximately 20% of invasive Breast Cancers (BCs) are characterized by Human Epidermal growth factor Receptor 2 (HER2) protein overexpression or HER2 gene amplification. HER2 represents a standard diagnostic test and a predictive biomarker for the use of HER2-directed treatments in patients with BC. At present, the HER2 Immunohistochemistry (IHC) assay is applied for screening purposes, and the In Situ Hybridization (ISH) test serves as a confirmation, when HER2 IHC results are equivocal. However, an accurate assessment and interpretation of the HER2 status can be complicated in many women with BC. These difficulties can be attributed to various factors such as HER2 Intratumoral Heterogeneity (ITH) and changes of HER2 in the process of BC metastatic progression or post neoadjuvant Chemotherapy (CHT). In particular, the status of biomarkers (e.g., HER2 and co-expressed Hormone Receptor (HR)) can be altered in patients with metastatic BC and such receptor changes influence the therapeutic responses and clinical outcomes. The goal of this article is to present challenges in the assessment of HER2 expression and to underscore a need for the biomarker status reevaluation in patients with metastatic BC. This mini-review also provides some insights into the interpretation of equivocal HER2 status in women with metastatic BC and discusses the impact of HER2 and HR biomarker conversions on therapeutic decision-making and the patient prognosis in metastatic BC. It is crucial to correctly interpret the HER2 biomarker status and to assess conversions of HER2 and HR in the BC metastatic lesions since timely detection of such alterations is critical to management modifications of individual patients with metastatic BC.