Impact of HER2 on prognosis and benefit from adjuvant chemotherapy in stage II/III gastric cancer patients: a multicenter observational study

Author:

Gao Xianchun12ORCID,Zhao Lulu3,Zhang Nannan1456ORCID,Han Weili1ORCID,Liu Kun1ORCID,Yan Junya1,Chen Ling7,Pan Yan1,Li Renlong1,Li Wenjiao1,Zhang Haohao1,Li Hongwei1,Wang Shibo1ORCID,Gao Xiaoliang1,Niu Penghui3,Wang Wanqing3,Ji Gang1,Zhao Qingchuan1,Lu Yuanyuan1ORCID,Li Zengshan7,Shang Lei2,Liang Han456,Wu Kaichun1ORCID,Deng Jingyu456ORCID,Chen Yingtai3ORCID,Nie Yongzhan1ORCID,

Affiliation:

1. State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases

2. Department of Health Statistics, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health

3. Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing

4. Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer

5. Key Laboratory of Cancer Prevention and Therapy

6. Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China

7. State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi’an

Abstract

Background: Human epidermal growth factor receptor 2 (HER2) is a well-developed therapeutic target in breast and gastric cancer (GC). However, the impact of HER2 on survival and benefit from fluorouracil-based adjuvant chemotherapy remains unclear in patients with GC. Materials and Methods: This multicenter cohort study involved 5622 consecutive stage II/III GC patients. HER2 expression was assessed prospectively via immunohistochemistry (IHC). The staining intensity was graded on a scale of 0 to 3+. An IHC score of 2+or 3+was defined as high expression, and a score of 3+was defined as overexpression. Results: HER2 overexpression was independently associated with a lower 5-year overall survival (OS) in stage II [hazard ratio (HR), 2.10; 95% CI: 1.41–3.11], but not in stage III GC (HR, 1.00; 95% CI, 0.82–1.20). Further analysis revealed that stage II patients with high HER2 expression showed a poorer response to chemotherapy than stage II patients with low HER2 expression (P interaction=0.024). The HRs for 5-year OS were 0.51 (95% CI, 0.38–0.70) for stage II patients with low HER2 expression, 0.58 (95% CI, 0.51–0.66) for stage III patients with low HER2 expression, 1.13 (95% CI, 0.61–2.09) for stage II patients with high HER2 expression, and 0.47 (95% CI, 0.36–0.61) for stage III patients with high HER2 expression. Conclusions: Fluorouracil-based adjuvant chemotherapy is insufficient for stage II GC patients with high HER2 expression, indicating that prospective trials are required to validate alternative HER2-targeted adjuvant therapies in the individuals above.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

General Medicine,Surgery

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