Genomic profiling and HER2-targeted therapy: a case series of Chinese salivary duct carcinoma patients and its clinical implications.

Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancers (SGCs). Currently, there is no approved targeted therapy for this devastating disease. This study aimed to identify actionable genomic alterations in Chinese patients with SDC and explore the clinical efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapies in this population. Somatic and genomic DNA were isolated from SDC samples and the corresponding peripheral blood controls, respectively. To explore the potential of targeted therapy, next-generation sequencing (NGS) was used to identify genomic alterations, especially mutations with clinical significance. The most prevalent driver mutations in this SDC cohort are TP53, HER2, PIK3CA, HRAS, and NF1. Except for TP53, the other four driver mutations are targetable. We identified three novel HER2 mutations (D769H, H878Y, and an exon 16 skipping mutation) in SDC, marking the first report of these mutations in this cancer type. Two metastatic SDC patients with HER2 amplification responded to HER2 tyrosine kinase inhibitor (TKI) pyrotinib and the combination of trastuzumab and pertuzumab, respectively. Our work underscores the potential of genomic profiling to guide precision therapy in SDC, with HER2-targeted treatments offering promising therapeutic avenues.