Prevalence of HER3 Expression in Pancreatic Cancer Patients Treated With Systemic Chemotherapy

Abstract

Background: Although activation of human epidermal growth factor receptor 3 (HER3) is linked to resistance to targeted therapies in several cancer types, the HER3 expression profile during pancreatic cancer treatment remains unknown. Aims: We evaluated the HER3 expression status after chemotherapy for pancreatic cancer and its association with clinicopathological features and clinical outcomes. Materials & Methods: We included patients with pancreatic cancer who underwent chemotherapy and whose post-treatment archival tissue specimens were collected. HER3 expression was retrospectively assessed by immunohistochemistry scoring (0, 1+, 2+, and 3+) of the membranous staining intensity. Results: HER3 expression after chemotherapy was evaluated in 41 patients, with matched-pair analysis in five patients before and after chemotherapy. HER3 expression was observed in most of the patients after chemotherapy, demonstrating IHC scores of ≥ 1+ and ≥ 2+ in 40 (98%) and 26 (63%) of 41 patients, respectively. Of the 38 patients with adenocarcinoma, the median overall survival in the HER3 (2+/3+) and HER3 (0/1+) groups was 21.0 and 17.1 months, respectively. The comparison of HER3 expression before and after chemotherapy performed in five cases revealed that scores changed from 2+/3+ to 0/1+ in one case, 0/1+ to 2+/3+ in another case, and remained at 2+/3+ in three cases. Cancer genome profiling tests in eight cases found no HER3 amplification or mutation, and seven of these cases had adenocarcinomas with KRAS and TP53 mutations. Conclusion: A high prevalence of HER3 expression was observed in pancreatic cancer patients after chemotherapy. Our findings indicate that HER3 is a potential therapeutic target for pancreatic cancer, deserving further clinical investigation.