Trastuzumab in combination with standard chemotherapy has been included in the guideline recommendations for human epidermal growth factor receptor 2 (HER2)–positive advanced-stage and recurrent endometrial carcinomas since 2019. A novel antibody drug conjugate, trastuzumab deruxtecan, gained tumor agnostic approval for HER2-positive metastatic solid tumors, including endometrial, ovarian, and cervical cancer in 2024.
To provide a detailed overview of HER2 protein expression, gene amplification, and mutation in gynecologic malignancies in light of the newly available anti-HER2 therapies. Tumor-specific HER2 testing and scoring algorithms are discussed, including the implications of the DESTINY-PanTumor02 trial results and the significance of the HER2-low tumor category.
Review of the literature and personal experience of the author.
The clinical indications and demand for HER2 testing in gynecologic malignancies beyond endometrial cancer are expanding. It is essential for practicing pathologists to stay up-to date on the latest clinical developments and use evidence-based HER2 testing and scoring criteria.
Author notes
Buza reports scientific consultant fees from Astra Zeneca/Daiichi Sankyo, Agilent, and GlaxoSmithKline.