Prognostic and Predictive Roles of HER2 Status in Non-Breast and Non-Gastroesophageal Carcinomas

The oncogene ERBB2, also known as HER2 or c-ERB2, is located on chromosome 17 (q12). It encodes a tyrosine kinase receptor, the human epidermal growth factor receptor 2 (HER2), involved in neoplastic proliferation, tumor angiogenesis, and invasiveness. Over the past years, the introduction of various anti-HER2 therapies has significantly improved outcomes for patients with HER2-positive breast and gastroesophageal carcinomas. More recently, the introduction of a new antibody-drug conjugate, that is trastuzumab deruxtecan, expanded the therapeutic options to low-HER2 breast and gastroesophageal tumors. HER2 protein overexpression is investigated using immunohistochemistry, gene amplification using fluorescence in situ hybridization, and gene mutation using next-generation sequencing. This review evaluated the predictive and prognostic role of HER2 status in various types of epithelial malignant cancers beyond breast and gastroesophageal cancers. We critically analyzed the key published studies, focusing on utilized scoring systems and assays used, and analyzed clinical parameters and therapeutic approaches. Although the evidence about prognostic and predictive roles of HER2 in carcinomas other than breast and gastroesophageal has been widely increasing over the last decade, it still remains investigational, revealing a tumor site-related prognostic and predictive value of the different types of HER2 alterations. However, standardized and validated scoring system assays have not been well-established for many organs.