HER2 as a potential biomarker guiding adjuvant chemotherapy in stage II colorectal cancer

Background: HER2 is a well-established therapeutic target in breast and gastric cancers, while the role of HER2 in colorectal cancer is unclear, and no studies have explored the impact of HER2 on the outcome of stage II colorectal cancer patients treated with 5-fluorouracial based adjuvant chemotherapy. Methods: We analyzed HER2 mRNA expression of 206 patients in GSE39582 dataset and explored the impact of HER2 expression on benefit from adjuvant chemotherapy for stage II colon cancer patients. We further validated the finding by retrospectively analyzing HER2 detection of immunohistochemistry in a cohort of 282 patients in Fudan University Shanghai Cancer Center (FUSCC). Results: In GSE39582 dataset, chemo-treated HER2-high patients had a better overall survival (OS) and relapse-free survival (RFS) versus chemo-naive HER2-high patients (5-year OS: 100% vs 69.5%, 5-year RFS: 100% and vs 64%, P = 0.027 and 0.025, respectively). On the contrary, chemo-treated HER2-low patients had a worse RFS compared with chemo-naIve HER2-low patients (5-year RFS: 65.6% vs 82.1%, P = 0.022). In FUSCC cohort, chemo-treated HER2-positive patients exhibited better OS vs chemo-naIve HER2-positive patients (5-year OS: 100% vs 73.8%, P < 0.001), and showed marginal evidence of a lower probability of recurrence (5-year RFS: 74.4% vs 58.7%, P = 0.072). After stratifying by mismatch repair (MMR) status, the results only kept consistency in patients with pMMR status. Conclusions: HER2-positve patients with stage II colorectal cancer can benefit from 5-fluorouracial based adjuvant chemotherapy, especially for patients with pMMR status. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.