title: The impact of concomitant genomic alterations on treatment outcome for trastuzumab therapy in HER2-positive gastric cancer.
abstract: Clinical benefit from trastuzumab and other anti-human epidermal growth factor receptor-2 (HER2) therapies in patients with HER2-positive gastric cancer (GC) remains limited by primary or acquired resistance. We aimed to investigate the impact of concomitant molecular alterations to HER2 amplification on the clinical outcome of trastuzumab-treated patients. Using immunohistochemistry (IHC), copy number variations (CNVs), and Ion Ampliseq Cancer Panel, we analyzed the status of concomitant alterations in 50 HER2-positive advanced GC patients treated with trastuzumab in combination with other chemotherapeutic agents. The percentage of tumor samples with at least one concomitant alteration was 40% as assessed by IHC, 16% by CNVs, and 64% by Ampliseq sequencing. Median progression-free survival (PFS) was 8.0 months (95% confidence interval, 4.8-11.3). Patients were divided into two subgroups according to PFS values with a cutoff point of 8 months; results show that concomitant genomic alterations do not correlate with trastuzumab response. However, CNVs of CCNE1 significantly correlated (p < 0.05) with a shorter survival time. Our findings indicate that additional alterations implemented for prediction of clinical benefit from HER2-targeting agents in GC remained unclear. Further studies will be needed to elucidate the role of each specific biomarker and to optimize therapeutic approaches.
authors: Division of Hematology-Oncology, Department of Medicine, Gastric Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-roGangnam-gu, Seoul 135-710, Korea.
authors: Ji Yun
authors: JY
authors: Lee
authors: 1] Center for Companion Diagnostics, Innovative Cancer Medicine Institute, Samsung Medical Center, Seoul, Korea [2] Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-roGangnam-gu, Seoul 135-710, Korea.
authors: Mineui
authors: M
authors: Hong
authors: Division of Hematology-Oncology, Department of Medicine, Gastric Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-roGangnam-gu, Seoul 135-710, Korea.
authors: Seung Tae
authors: ST
authors: Kim
authors: Division of Hematology-Oncology, Department of Medicine, Gastric Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-roGangnam-gu, Seoul 135-710, Korea.
authors: Se Hoon
authors: SH
authors: Park
authors: Division of Hematology-Oncology, Department of Medicine, Gastric Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-roGangnam-gu, Seoul 135-710, Korea.
authors: Won Ki
authors: WK
authors: Kang
authors: 1] Center for Companion Diagnostics, Innovative Cancer Medicine Institute, Samsung Medical Center, Seoul, Korea [2] Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-roGangnam-gu, Seoul 135-710, Korea.
authors: Kyoung-Mee
authors: KM
authors: Kim
authors: Division of Hematology-Oncology, Department of Medicine, Gastric Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-roGangnam-gu, Seoul 135-710, Korea.
authors: Jeeyun
authors: J
authors: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D056915:DNA Copy Number Variations; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000068878:Trastuzumab / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab