Response to Anti-HER2-Based Treatment in a Patient with Bladder Adenocarcinoma Harboring HER2 Amplification and S310F Mutation Discovered by Next-Generation Sequencing: A Case Report

Abstract

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.

Figure 1

Pathologic findings of the primary tumor and the pulmonary lesion specimen after trastuzumab-based therapy. (A) Hematoxylin and eosin staining of the primary tumor revealed bladder adenocarcinoma (magnification ×200). (B) Hematoxylin and eosin staining of the pulmonary lesion specimen after trastuzumab-based therapy revealed adenocarcinoma, indicating that it was a metastasis of bladder adenocarcinoma (magnification ×200). (C) The primary tumor exhibited strong positive immunohistochemical staining for HER2 (3+) (magnification ×200). (D) The pulmonary lesion specimen after trastuzumab-based therapy exhibited positive immunohistochemical staining for HER2 (2+) (magnification ×200).

Figure 2

Chest CT scans before and after trastuzumab-based therapy. (A) Before trastuzumab-based therapy (March 30, 2018), a CT scan showed a lesion in the left lower lung lobe (white arrow). (B) The disease reached partial remission after 2 cycles of trastuzumab-based treatment (May 25, 2018), the mass was reduced significantly (white arrow). (C) Disease progression after trastuzumab-based therapy for six months, enlargement of the mass (white arrow) was observed on October 23, 2018.

Figure 3

Analysis results from the STRING website. (A) Relationship of seven mutant genes before trastuzumab-based therapy. (B) Relationship of five mutant genes after trastuzumab-based therapy.