HER2 Testing in Breast and Gastric Cancer with CDH1 Germline Mutations

The role of human epidermal growth factor receptor-2 (HER2) is involved in epithelial cells growth and differentiation and has been widely studied in a plethora of cancers. HER2 alterations have been known to drive tumor cell proliferation, migration and reduce apoptosis. Tumor expression of HER2 marker has prognostic and predictive significance in breast and gastroesophageal cancers. These two cancer types may arise as constituents of hereditary diffuse gastric cancer syndrome (HDGS), which is linked to E-cadherin coding CDH1 gene alterations. Precisely, HDGS features a high prevalence of diffuse gastric and lobular breast cancers. HER2 alterations may simultaneously occur with CDH1 mutations; however, the role of HER2 overexpression in these patients and two biomarkers’ relationship is not fully understood. In this chapter, we sought to provide a comprehensive overview of the biological role of HER2 biomarker and current testing guidelines in breast and gastric cancer, in association with genetic CDH1 alterations.