Hiroshi Saeki1, Eiji Oki2, Tomomi Kashiwada3, Takaaki Arigami4, Akitaka Makiyama5, Masaaki Iwatsuki6, Yukiya Narita7, Hironaga Satake8, Yoshiko Matsuda9, Hideto Sonoda10, Mototsugu Shimokawa11, Yoshihiko Maehara12. 1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan. 2. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan. Electronic address: okieiji@surg2.med.kyushu-u.ac.jp. 3. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan. 4. Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Japan. 5. Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Japan. 6. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan. 7. Department of Clinical Oncology, Aichi Cancer Center Hospital, Japan. 8. Department of Medical Oncology, Kobe City Medical Center General Hospital, Japan. 9. Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Japan. 10. Department of Surgery, Imari Arita Kyoritsu Hospital, Japan. 11. Clinical Research Institute, Cancer Biostatistics Laboratory, National Kyushu Cancer Center, Fukuoka, Japan. 12. Kyushu Central Hospital, Fukuoka, Japan.
Abstract
BACKGROUND: Anti-HER2 therapy has not demonstrated a survival advantage in the second-line setting of patients with HER2-positive gastric cancer. We conducted this study to assess changes in HER2 status and to identify possible biomarkers for acquired resistance after the use of trastuzumab as the first-line therapy. PATIENTS AND METHODS: Patients with advanced or recurrent HER2-positive gastric adenocarcinoma who were diagnosed with progressive disease after the first-line trastuzumab-based therapy and developed pathologically confirmed adenocarcinoma within 3 months after completion of trastuzumab-based therapy were enrolled in this study. We collected re-biopsied samples from the HER2-positive patients who had developed resistance to trastuzumab and re-evaluated their HER2 status. Amplification of EGFR and c-met, as well as PIK3CA mutation, were comparatively analysed when samples were available. RESULTS: Among 33 eligible patients, loss of HER2 was identified in 20 patients (60.6%) with refractory disease. Immunohistochemistry showed that the rate of HER2 overexpression was greatly reduced after therapy (pre-HER2 3+: 24 [72.7%] vs. post-HER2 3+: 13 [39.4%]). We found that the use of fixatives other than 10% neutral buffered formalin significantly reduced the HER2-positive rate. EGFR amplification, c-met amplification and PIK3CA mutation before and after trastuzumab-based therapy were observed in 10.3% and 3.8%, 17.9% and 4.2% and 4.0% and 4.2% of cases, respectively. CONCLUSION: Re-evaluation of HER2 status is needed to determine the appropriate use of anti-HER2-targeted therapy after disease progression. Our results also highlight the importance of formalin fixation conditions for HER2 testing.
BACKGROUND: Anti-HER2 therapy has not demonstrated a survival advantage in the second-line setting of patients with HER2-positive gastric cancer. We conducted this study to assess changes in HER2 status and to identify possible biomarkers for acquired resistance after the use of trastuzumab as the first-line therapy. PATIENTS AND METHODS: Patients with advanced or recurrent HER2-positive gastric adenocarcinoma who were diagnosed with progressive disease after the first-line trastuzumab-based therapy and developed pathologically confirmed adenocarcinoma within 3 months after completion of trastuzumab-based therapy were enrolled in this study. We collected re-biopsied samples from the HER2-positive patients who had developed resistance to trastuzumab and re-evaluated their HER2 status. Amplification of EGFR and c-met, as well as PIK3CA mutation, were comparatively analysed when samples were available. RESULTS: Among 33 eligible patients, loss of HER2 was identified in 20 patients (60.6%) with refractory disease. Immunohistochemistry showed that the rate of HER2 overexpression was greatly reduced after therapy (pre-HER2 3+: 24 [72.7%] vs. post-HER2 3+: 13 [39.4%]). We found that the use of fixatives other than 10% neutral buffered formalin significantly reduced the HER2-positive rate. EGFR amplification, c-met amplification and PIK3CA mutation before and after trastuzumab-based therapy were observed in 10.3% and 3.8%, 17.9% and 4.2% and 4.0% and 4.2% of cases, respectively. CONCLUSION: Re-evaluation of HER2 status is needed to determine the appropriate use of anti-HER2-targeted therapy after disease progression. Our results also highlight the importance of formalin fixation conditions for HER2 testing.
Authors: Nicholas C DeVito; Colm Kelleher; Kyle C Strickland; James Abbruzzese; Carey Anders; Brent A Hanks; Jingquan Jia; Niharika B Mettu; Michael A Morse; Margot O'Neill; Hope Uronis; Yousuf Zafar; John H Strickler Journal: AME Case Rep Date: 2021-04-25
Authors: Jayati Chakrabarti; Vivien Koh; Nina Steele; Jennifer Hawkins; Yoshiaki Ito; Juanita L Merchant; Jiang Wang; Michael A Helmrath; Syed A Ahmad; Jimmy Bok Yan So; Wei Peng Yong; Yana Zavros Journal: Cancers (Basel) Date: 2021-12-07 Impact factor: 6.575