HER2-Positive Serous Endometrial Cancer Treatment: Current Clinical Practice and Future Directions

The most common histological subtypes of endometrial cancer consist of endometrioid and uterine serous carcinoma, with the latter being more aggressive and accompanied by poor prognosis. Human epidermal growth factor receptor 2 (HER2) is a transmembrane tyrosine kinase receptor associated with cell proliferation, differentiation, and survival. HER2 positivity can be diagnosed in many solid tumors. It has been found that approximately one-third of the patients diagnosed with serous carcinoma may overexpress HER2/neu protein and/or show the amplification of the c-erBb2 gene. The prognostic and predictive value of HER2 biomarker is nowadays highlighted and the updates of HER2-directed treatment offer new opportunities for improved efficacy and survival. A number of HER2-targeted therapies have become available in recent years and have had promising results, prompting full drug approvals and additional investigation in many cancer types, among which is endometrial cancer. Data from clinical trials combining classical chemotherapy with anti-HER2 agents, mainly trastuzumab, alone or in combination with pertuzumab, do exist and have been incorporated into international guidelines. Moreover, further research with antibody-drug conjugates and tyrosine kinase inhibitors is being conducted. Acquired resistance remains an important problem, and its underlying mechanisms in endometrial cancer are mostly unknown. Studies exploring earlier use of Her2-directed therapy are also on the way. The purpose of this literature review is to describe the available therapies in the current clinical practice and the most prominent research data regarding the future. In any case, a number of unmet medical needs do exist for HER2-positive serous endometrial cancer, and additional research and studies are warranted to provide further understanding and improved outcomes for this tumor type.