Trastuzumab Therapy and Genotype

Trastuzumab (brand name, Herceptin) is a monoclonal antibody used in the treatment of breast and gastric/gastroesophageal cancer. It targets an epidermal growth factor receptor encoded by the gene, which is commonly referred to as the gene. Multiple biosimilar products to Herceptin are now available: Kanjinti, Trazimera, Ontruzant, Herzuma and Ogivri. The gene is overexpressed in 15–20% of breast cancers and 15–20% of gastric and esophageal cancers. Overall, “HER2 positive” tumors are associated with a faster rate of growth and—in some cases—a poorer prognosis in absence of anti-HER2 therapy. The use of trastuzumab in treatment regimens improves outcomes, with limited adverse effects that include cardiac toxicity. The FDA-approved drug label states that trastuzumab should only be used to treat individuals with tumors that have either HER2 protein overexpression or gene amplification, as determined by an accurate and validated FDA-approved assay, specific for the type of tumor tested (breast or gastric) (Table 1)(1). The FDA-approved drug label for all trastuzumab biosimilars describes only the use of trastuzumab in adjuvant treatment of breast cancer, though its efficacy in neoadjuvant care for breast cancer (reviewed in part by (2)) and esophageal adenocarcinoma (3) has also been documented. The most recent update (2018) of the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines continues to state that all newly diagnosed individuals with breast cancer must have an HER2 test performed. Individuals who then develop metastatic disease must have an HER2 test performed in a metastatic site, if tissue sample is available (4).