Purpose: HER2 overexpression has been identified in approximately 14% of bladder adenocarcinomas. However, until now, there has been no approved standard targeted therapy for bladder adenocarcinoma patients harboring HER2  genetic alteration.
Case Presentation: We presented a case of a 64-year-old man who was diagnosed with bladder adenocarcinoma, and lung metastasis was confirmed less than one year after initial bladder surgery. The patient received systemic chemotherapy and antiangiogenetic treatment, but the tumor continued to progress. The patient underwent next-generation sequencing (NGS) to seek potential treatment opportunities. HER2  amplification, approximately 7 times, was discovered together with the S310F mutation (mutant abundance 90%). The patient then received late-line treatment with trastuzumab and albumin-bound paclitaxel. A partial response was confirmed two months later. Trastuzumab-based therapy was continued for 8 cycles, and the progression-free survival period was 6 months. NGS was performed on a rebiopsy, and the result showed no amplification of HER2 , and the S310F mutant abundance was reduced to 27.9%.
Conclusion: This is the first case report describing a bladder adenocarcinoma patient harboring HER2  amplification who responded to trastuzumab. NGS is of great potential in the selection of bladder adenocarcinoma patients suitable for anti-HER2 therapy. The genetic change after treatment also implied possible mechanisms of resistance to trastuzumab-based therapy, which requires more investigation.
Keywords: bladder adenocarcinoma, human epidermal growth factor receptor 2, next-generation sequencing, trastuzumab