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Effect of HER2/CEP17 ratio on survival in metastatic HER2-positive gastric cancer, multicenter study

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Abstract

Aim

HER2-positive metastatic gastric cancer is still a highly fatal disease despite advances. We aimed to investigate the relationship between HER2/CEP17 ratio and survival in patients with HER2-positive metastatic gastric cancer.

Methods

A total of 99 patients from 8 different centers in Turkey were included in the study. Patients with HER2-positive metastatic gastric cancer and whose HER2/CEP17 ratio was examined were included in the study. Patients were divided into two groups according to HER2/CEP17 values, and survival analysis was performed.

Results

The median age was 64 (24–83) years. There were 74 (74.8%) male and 25 (25.2%) female patients. OS in the high HER2/CEP17 ratio group was 21.97 months (95% CI: 16.36–27.58), and in the low ratio group was 16.17 months (95% CI: 10.95–21.38) (p = 0.015). OS was 17.7 months (95% CI: 7.02–28.37) in the high HER2 gene copy number group and 10.13 months (5.55–14.71) in the group with low copy number (p = 0.03). PFS was 10.94 months (95% CI: 7.55–14.33) in the group with high HER2 gene copy number and 7.56 months (4.62–10.49) in the low copy number group (p = 0.06).

Conclusion

Patients with both high HER2 gene amplification and high HER2/CEP17 ratio had better OS. The PFS of the group with high HER2 gene amplification was also better. To our knowledge, this is the first study in the literature showing that the HER2/CEP17 ratio affects survival in patients with metastatic gastric cancer.

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References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.

    Article  PubMed  Google Scholar 

  2. Qiu H, Cao S, Xu R. Cancer incidence, mortality, and burden in China: a time-trend analysis and comparison with the United States and United Kingdom based on the global epidemiological data released in 2020. Cancer Commun (Lond). 2021;41(10):1037–48.

    Article  PubMed  Google Scholar 

  3. Zaanan A, Bouche O, De La Fouchardiere C, Samalin-Scalzi E, Le Malicot K, Pernot S, et al. LBA77 5-fluorouracil and oxaliplatin with or without docetaxel in the first-line treatment of HER2 negative locally advanced (LA) unresectable or metastatic gastric or gastro-esophageal junction (GEJ) adenocarcinoma (GASTFOX-PRODIGE 51): a randomized phase III trial sponsored by the FFCD. Ann Oncol. 2023;34:S1318.

    Article  Google Scholar 

  4. Ma J, Lyu H, Huang J, Liu B. Targeting of erbB3 receptor to overcome resistance in cancer treatment. Mol Cancer. 2014;13(1):105.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Moasser MM. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene. 2007;26(45):6469–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Abrahao-Machado LF, Scapulatempo-Neto C. HER2 testing in gastric cancer: an update. World J Gastroenterol. 2016;22(19):4619–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97.

    Article  CAS  PubMed  Google Scholar 

  8. Liu Z, Shi M, Li X, Song S, Liu N, Du H, et al. HER2 copy number as predictor of disease-free survival in HER2-positive resectable gastric adenocarcinoma. J Cancer Res Clin Oncol. 2021;147(5):1315–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pietrantonio F, Manca P, Bellomo SE, Corso S, Raimondi A, Berrino E, et al. HER2 copy number and resistance mechanisms in patients with HER2-positive advanced gastric cancer receiving initial trastuzumab-based therapy in JACOB trial. Clin Cancer Res. 2023;29(3):571–80.

    Article  CAS  PubMed  Google Scholar 

  10. Papouchado BG, Myles J, Lloyd RV, Stoler M, Oliveira AM, Downs-Kelly E, et al. Silver in situ hybridization (SISH) for determination of HER2 gene status in breast carcinoma: comparison with FISH and assessment of interobserver reproducibility. Am J Surg Pathol. 2010;34(6):767–76.

    Article  PubMed  Google Scholar 

  11. Rüschoff J, Dietel M, Baretton G, Arbogast S, Walch A, Monges G, et al. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch. 2010;457(3):299–307.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Greenwell K, Hussain L, Lee D, Bramlage M, Bills G, Mehta A, et al. Complete pathologic response rate to neoadjuvant chemotherapy increases with increasing HER2/CEP17 ratio in HER2 overexpressing breast cancer: analysis of the National Cancer Database (NCDB). Breast Cancer Res Treat. 2020;181(2):249–54.

    Article  CAS  PubMed  Google Scholar 

  13. Fuchs CS, Mayer RJ. Gastric carcinoma. N Engl J Med. 1995;333(1):32–41.

    Article  CAS  PubMed  Google Scholar 

  14. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20.

    Article  CAS  PubMed  Google Scholar 

  15. Coburn NG, Swallow CJ, Kiss A, Law C. Significant regional variation in adequacy of lymph node assessment and survival in gastric cancer. Cancer. 2006;107(9):2143–51.

    Article  PubMed  Google Scholar 

  16. Wang J, Sun Y, Bertagnolli MM. Comparison of gastric cancer survival between Caucasian and Asian patients treated in the United States: results from the Surveillance Epidemiology and End Results (SEER) database. Ann Surg Oncol. 2015;22(9):2965–71.

    Article  PubMed  Google Scholar 

  17. Terashima M, Kitada K, Ochiai A, Ichikawa W, Kurahashi I, Sakuramoto S, et al. Impact of expression of human epidermal growth factor receptors EGFR and ERBB2 on survival in stage II/III gastric cancer. Clin Cancer Res. 2012;18(21):5992–6000.

    Article  CAS  PubMed  Google Scholar 

  18. Okines AF, Thompson LC, Cunningham D, Wotherspoon A, Reis-Filho JS, Langley RE, et al. Effect of HER2 on prognosis and benefit from peri-operative chemotherapy in early oesophago-gastric adenocarcinoma in the MAGIC trial. Ann Oncol. 2013;24(5):1253–61.

    Article  CAS  PubMed  Google Scholar 

  19. Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, et al. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14(6):490–9.

    Article  CAS  PubMed  Google Scholar 

  20. Wagner AD, Syn NL, Moehler M, Grothe W, Yong WP, Tai BC, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2017;8(8): Cd004064.

    PubMed  Google Scholar 

  21. AktürkEsen S, Ergun Y, Erol C, Arikan R, Er MM, Atci MM, et al. First-line treatment of patients with HER2-positive metastatic gastric and gastroesophageal junction cancer. Bosn J Basic Med Sci. 2022;22(5):818–25.

    Google Scholar 

  22. Ajani JA, D’Amico TA, Bentrem DJ, Chao J, Cooke D, Corvera C, et al. Gastric cancer, version 2.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2022;20(2):167–92.

    Article  CAS  Google Scholar 

  23. Chua TC, Merrett ND. Clinicopathologic factors associated with HER2-positive gastric cancer and its impact on survival outcomes–a systematic review. Int J Cancer. 2012;130(12):2845–56.

    Article  CAS  PubMed  Google Scholar 

  24. Gomez-Martin C, Plaza JC, Pazo-Cid R, Salud A, Pons F, Fonseca P, et al. Level of HER2 gene amplification predicts response and overall survival in HER2-positive advanced gastric cancer treated with trastuzumab. J Clin Oncol. 2013;31(35):4445–52.

    Article  CAS  PubMed  Google Scholar 

  25. Lander EM, Rappazzo KC, Huang LC, Hu JR, Chen H, Shyr Y, et al. Using the HER2/CEP17 fish ratio to predict pathologic complete response following neoadjuvant anti-HER2 doublet therapy in HER2+ breast cancer. Oncologist. 2023;28(2):123–30.

    Article  PubMed  Google Scholar 

  26. Park JH, Yeo JH, Kim YS, Park I, Ahn HK, Shin DB, et al. Predictive roles of HER2 gene amplification and neutrophil-to-lymphocyte ratio on survival in HER2-positive advanced gastric cancer treated with trastuzumab-based chemotherapy. Am J Clin Oncol. 2021;44(6):232–8.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Oncology, Ankara City Hospital, Ankara, Turkey

    Serhat Sekmek, Irfan Karahan, Gokhan Ucar, Furkan Ceylan, Dogan Bayram, Ismet Seven, Burak Civelek, Bulent Yalcin & Dogan Uncu

  2. Department of Medical Oncology, Ankara University, Ankara, Turkey

    Hatice Bölek & Yüksel Ürün

  3. Department of Medical Oncology, Gazi University, Ankara, Turkey

    Kadriye Bir Yücel & Ozan Yazici

  4. Department of Medical Oncology, UHS Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey

    Ahmet Kadioglu & Cengiz Karacin

  5. Department of Medical Oncology, Dokuz Eylul University, Izmir, Turkey

    Kubra Canaslan & Elif Atag

  6. Department of Medical Oncology, İstanbul Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey

    Serhat Demirer & Gokmen Umut Erdem

  7. Department of Medical Oncology, Antalya City Hospital, Antalya, Turkey

    Yakup Ergun

  8. Department of Medical Oncology, Ankara Etlik City Hospital, Ankara, Turkey

    Mehmetcan Atak

  9. Department of Medical Oncology, Hacettepe University, Ankara, Turkey

    Baris Koksal

  10. Department of Pathology, Ankara City Hospital, Ankara, Turkey

    Merve Meryem Kiran & Duriye Ozer Turkay

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  1. Serhat Sekmek
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  2. Irfan Karahan
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Correspondence to Serhat Sekmek.

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None of the authors has any significant direct or indirect commercial or financial incentives associated with the publication of the article. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.

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Sekmek, S., Karahan, I., Ucar, G. et al. Effect of HER2/CEP17 ratio on survival in metastatic HER2-positive gastric cancer, multicenter study. Clin Transl Oncol (2024). https://doi.org/10.1007/s12094-024-03410-x

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