Abstract
Purpose
To investigate the role of HER2 positivity in prognosis and unresponsiveness to anti-EGFR therapy for colorectal cancer.
Methods
Patients who underwent primary CRC tumor resection were included. HER2 status of CRC was confirmed by immunohistochemistry and fluorescence in situ hybridization tests. Comparison of survival analysis between HER2 positivity and negativity was evaluated by a stratified log-rank test and summarized with the use of Kaplan–Meier and Cox proportional hazards methods. The treatment effects of cetuximab were further compared in full subgroup analyses.
Result
1240 patients were enrolled, including 763 with stage I-III CRC and 477 with stage IV CRC. 57 (4.6%) CRC patients presented HER2 positivity in the entire cohort. The survival analysis showed that patients with HER2 positivity had significantly worse disease-free survival and overall survival in stage III and IV CRC. The multivariable analysis also confirmed that HER2 positivity was a significantly independent risk factor in stage III and IV CRC. Univariate and multivariable survival analysis showed no prognostic significance of HER2 positivity in stage I–II CRC patients. Prespecified subgroup analysis showed no favorable trends in progression-free survival and overall survival for cetuximab in the patients with HER2 positivity, KRAS/NRAS/BRAF wild-type metastatic CRC (interaction P values = 0.005 and 0.014).
Conclusion
For stage III and IV CRC patients, HER2 positivity was confirmed as an independent prognostic risk factor. It could help predict the unresponsiveness to anti-EGFR therapy for metastatic CRC.
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Data availability
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
Supported by The National Natural Science Foundation of China (82072678, 82072653, 81372315); Shanghai Science and Technology Committee Project (19511121301, 17411951300); Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive (17DZ2252600); The National Key R&D Program of China (2017YFC0908200).
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(1) Conception/design: WH, YC, WC, LR, YW, JX; (2) Provision of study material or patients: WH, YC, WC, LR, YW, JX; (3) Collection and/or assembly of data: WH, YC, WC, LR, WT, PZ, QW; (4) Data analysis and interpretation: WH, YC, PZ, QW, TL, YL; (5) Manuscript writing: WH, YC, WC, LR; (6) Final approval of manuscript: WH, YC, WC, LR, WT, PZ, QW, TL, YL, YW, JX.
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Approved by the Clinical Research Ethics Committee of Zhongshan Hospital, Fudan University.
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Huang, W., Chen, Y., Chang, W. et al. HER2 positivity as a biomarker for poor prognosis and unresponsiveness to anti-EGFR therapy in colorectal cancer. J Cancer Res Clin Oncol 148, 993–1002 (2022). https://doi.org/10.1007/s00432-021-03655-x
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DOI: https://doi.org/10.1007/s00432-021-03655-x