Abstract 3405: Changes in HER3 expression associated with chemotherapy for pancreatic cancer
Authors: Satake Tomoyuki , Morizane Chigusa , Okada Mao , Nishioka Mariko , Hiraoka Nobuyoshi , Nara Satoshi , Kakegawa Tomoya , Kobayashi Maki , Koyama Kumiko , Esaki Minoru , Okusaka Takuji 
Published: April 2023

Abstract
Background: Currently, intense efforts towards the development of targeted therapy, including anti-HER3 strategies for cancer treatment, are being made. Recently, HER3 activation was linked to resistance to targeted therapies (EGFR/HER2/MEK/RAF) and hormonal therapy by upregulating HER3 expression after those treatments in several cancer types. However, HER3 expression profile in pancreatic cancer treatment is still unknown. Here, we evaluated the status of HER3 expression after chemotherapy for pancreatic cancer.
Methods: Patients with pancreatic cancer who underwent chemotherapy between January 2010 and June 2020 and from whom post-treatment archival tissue specimens were collected were included in this study. All resectable and locally advanced cases were evaluated using resected specimens, and all metastatic cases were evaluated using biopsy specimens. In patients from whom both pre- and post-chemotherapy specimens were collected, changes in HER3 expression status before and after treatment were immunohistochemically evaluated by using HER3/ErbB3 (D22C5) XP Rabbit mAb (Cell Signaling Technology) as a primary antibody. IHC scoring (0, 1+, 2+, 3+) of membranous staining intensity was performed according to HER2 IHC gastric scoring guideline.
Results: Post-chemotherapy HER3 expression was evaluable in 41 patients, comprising 12, 14, 14, and 1 case as HER3 3+, 2+, 1+ and 0, respectively. In the HER3 3+/2+ and 1+/0 groups, tumor localization was 69%/67% in the pancreatic head, 23%/13% in the pancreatic body, and 8%/20% in the pancreatic tail; tumor stage was resectable (post-neoadjuvant status) 46%/20%, locally advanced 42%/47%, and metastatic 12%/33%; the median tumor size was 30 mm/35 mm; CEA elevation was 23%/20% and CA19-9 elevation was 69%/73%; treatment regimens were FOLFIRINOX 23%/40%, gemcitabine + nab-paclitaxel 19%/0%, gemcitabine + S-1 (neoadjuvant setting) 42%/27%, and the other chemotherapy 4%/20%, respectively. HER3 expression was able to be evaluated before and after chemotherapy in 5 cases: HER3 IHC score changed from 3+/2+ to 1+/0 for 1 case, from 1+/0 to 3+/2+ for 1 case and maintained at 3+/2+ for 3 cases. The median overall survival was 19.6 and 20.5 months in the HER3 3+/2+ and HER3 1+/0 groups, respectively (P = 0.965).
Conclusion: HER3 expression with 3+/2+ is observed in 63% of pancreatic cancer patients, and HER3-expressing pancreatic cancer is of great interest as a therapeutic target. HER3 expression status may change before and after cytotoxic combination therapy in some cases of pancreatic cancer.
Citation Format: Tomoyuki Satake, Chigusa Morizane, Mao Okada, Mariko Nishioka, Nobuyoshi Hiraoka, Satoshi Nara, Tomoya Kakegawa, Maki Kobayashi, Kumiko Koyama, Minoru Esaki, Takuji Okusaka. Changes in HER3 expression associated with chemotherapy for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3405.