Wenbai Huang1,2, Yijiao Chen1,2, Wenju Chang1,2,3, Li Ren1,2,3,4, Wentao Tang1,2, Peng Zheng1,2, Qi Wu1,2, Tianyu Liu1,2, Yu Liu1,2, Ye Wei5,6,7,8, Jianmin Xu9,10,11,12. 1. Department of General Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, People's Republic of China. 2. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. 3. Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, China. 4. Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. 5. Department of General Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, People's Republic of China. 13818661815@126.com. 6. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. 13818661815@126.com. 7. Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, China. 13818661815@126.com. 8. Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. 13818661815@126.com. 9. Department of General Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, People's Republic of China. xujmin@aliyun.com. 10. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. xujmin@aliyun.com. 11. Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, China. xujmin@aliyun.com. 12. Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. xujmin@aliyun.com.
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.
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.
Authors: Kathryn L Harper; Maria Soledad Sosa; David Entenberg; Hedayatollah Hosseini; Julie F Cheung; Rita Nobre; Alvaro Avivar-Valderas; Chandandaneep Nagi; Nomeda Girnius; Roger J Davis; Eduardo F Farias; John Condeelis; Christoph A Klein; Julio A Aguirre-Ghiso Journal: Nature Date: 2016-12-14 Impact factor: 49.962
Authors: Carmen J Allegra; R Bryan Rumble; Stanley R Hamilton; Pamela B Mangu; Nancy Roach; Alexander Hantel; Richard L Schilsky Journal: J Clin Oncol Date: 2015-10-05 Impact factor: 44.544
Authors: Lena-Christin Conradi; Hanna Styczen; Thilo Sprenger; Hendrik A Wolff; Claus Rödel; Manuel Nietert; Kia Homayounfar; Jochen Gaedcke; Julia Kitz; Recca Talaulicar; Heinz Becker; Michael Ghadimi; Peter Middel; Tim Beissbarth; Josef Rüschoff; Torsten Liersch Journal: Am J Surg Pathol Date: 2013-04 Impact factor: 6.394
Authors: S Kapitanović; S Radosević; M Kapitanović; S Andelinović; Z Ferencić; M Tavassoli; D Primorać; Z Sonicki; S Spaventi; K Pavelic; R Spaventi Journal: Gastroenterology Date: 1997-04 Impact factor: 22.682
Authors: Andrea Bertotti; Giorgia Migliardi; Francesco Galimi; Francesco Sassi; Davide Torti; Claudio Isella; Davide Corà; Federica Di Nicolantonio; Michela Buscarino; Consalvo Petti; Dario Ribero; Nadia Russolillo; Andrea Muratore; Paolo Massucco; Alberto Pisacane; Luca Molinaro; Emanuele Valtorta; Andrea Sartore-Bianchi; Mauro Risio; Lorenzo Capussotti; Marcello Gambacorta; Salvatore Siena; Enzo Medico; Anna Sapino; Silvia Marsoni; Paolo M Comoglio; Alberto Bardelli; Livio Trusolino Journal: Cancer Discov Date: 2011-09-02 Impact factor: 39.397