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The relationship between brain metastasis and HER2 expression status in gastric cancer

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Abstract

Background

Brain metastasis (BM) in gastric cancer (GC) is underestimated, and human epidermal growth factor receptor 2 (HER2) overexpression is a durable poor prognostic factor. We explored the relationship between the two and made a survival analysis.

Methods

HER2 expression and BM status were collected from GC patients who were diagnosed between December 2009 and May 2021. We collected GC patients diagnosed between 2010 and 2016 from the SEER database. The primary endpoint was survival from the diagnosis of BM. Multivariable logistic regression was used to determine potential risk factors of BM at diagnosis in SEER database. Survival analysis was performed using the Kaplan–Meier method.

Result

There were 513 HER2-positive GC patients, including 16 (3.1%) with BM. Among 38 brain metastasis GC patients we collected, 16 (42.1%) patients were HER2 positive. We collected 34,199 GC patients from the SEER database and there were 260 (0.76%) patients with BM at diagnosis. GC patients that are male, white, of younger age, with primary lesions located in the proximal stomach or with distant lymph nodes, liver, bone, or lung metastasis are more likely to develop BM. The median overall survival time from diagnosis of BM was 12.73 months, and the survival time from brain metastasis of HER2-positive patients was numerically shorter, though the difference was not significant (5.30 months vs.16.13 months, P = 0.28.)

Conclusion

The incidence of BM in patients with HER2-positive gastric cancer is 4.08 times higher than that in general patients. The median overall survival time from BM is shorter for HER2-positive patients.

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Data availability

The data that support the findings of this study are available from the corresponding author, QMZ and YDJ, upon reasonable request.

References

  1. Thrift AP, El-Serag HB. Burden of gastric cancer. Clin Gastroenterol Hepatol. 2020;18(3):534–42. https://doi.org/10.1016/j.cgh.2019.07.045.

    Article  PubMed  Google Scholar 

  2. Yu M, Zheng HC, Xia P, Takahashi H, Masuda S, Takano Y, et al. Comparison in pathological behaviours & prognosis of gastric cancers from general hospitals between China & Japan. Indian J Med Res. 2010;132:295–302.

    PubMed  Google Scholar 

  3. Go PH, Klaassen Z, Meadows MC, Chamberlain RS. Gastrointestinal cancer and brain metastasis: a rare and ominous sign. Cancer. 2011;117(16):3630–40. https://doi.org/10.1002/cncr.25940.

    Article  PubMed  Google Scholar 

  4. Qiu MZ, Shi SM, Chen ZH, Yu HE, Sheng H, Jin Y, et al. Frequency and clinicopathological features of metastasis to liver, lung, bone, and brain from gastric cancer: a SEER-based study. Cancer Med. 2018;7(8):3662–72. https://doi.org/10.1002/cam4.1661.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hofmann M, Stoss O, Shi D, Buttner R, van de Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52(7):797–805. https://doi.org/10.1111/j.1365-2559.2008.03028.x.

    Article  CAS  PubMed  Google Scholar 

  6. Hsu JT, Chen TC, Tseng JH, Chiu CT, Liu KH, Yeh CN, et al. Impact of HER-2 overexpression/amplification on the prognosis of gastric cancer patients undergoing resection: a single-center study of 1,036 patients. Oncologist. 2011;16(12):1706–13. https://doi.org/10.1634/theoncologist.2011-0199.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Sheng WQ, Huang D, Ying JM, Lu N, Wu HM, Liu YH, et al. HER2 status in gastric cancers: a retrospective analysis from four Chinese representative clinical centers and assessment of its prognostic significance. Ann Oncol. 2013;24(9):2360–4. https://doi.org/10.1093/annonc/mdt232.

    Article  CAS  PubMed  Google Scholar 

  8. 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. https://doi.org/10.1016/S0140-6736(10)61121-X.

    Article  CAS  PubMed  Google Scholar 

  9. Berghoff A, Bago-Horvath Z, De Vries C, Dubsky P, Pluschnig U, Rudas M, et al. Brain metastases free survival differs between breast cancer subtypes. Br J Cancer. 2012;106(3):440–6. https://doi.org/10.1038/bjc.2011.597.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49. https://doi.org/10.1111/apm.1965.64.1.31.

    Article  CAS  PubMed  Google Scholar 

  11. Minisini AM, Moroso S, Gerratana L, Giangreco M, Iacono D, Poletto E, et al. Risk factors and survival outcomes in patients with brain metastases from breast cancer. Clin Exp Metastasis. 2013;30(8):951–6. https://doi.org/10.1007/s10585-013-9594-5.

    Article  CAS  PubMed  Google Scholar 

  12. Ahn HK, Park YH, Lee SJ, Park S, Maeng CH, Park W, et al. Clinical implication of time to brain metastasis (TTBM) according to breast cancer subtypes. Springerplus. 2013;2(1):136. https://doi.org/10.1186/2193-1801-2-136.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kuksis M, Gao Y, Tran W, Hoey C, Kiss A, Komorowski AS, et al. The incidence of brain metastases among patients with metastatic breast cancer: a systematic review and meta-analysis. Neuro Oncol. 2021;23(6):894–904. https://doi.org/10.1093/neuonc/noaa285.

    Article  PubMed  Google Scholar 

  14. Blay C, Chiforeanu DC, Boucher E, Cabillic F, Desgrippes R, Leconte B, et al. Incidence of brain metastases in HER2+ gastric or gastroesophageal junction adenocarcinoma. Acta Oncol. 2015;54(10):1833–5. https://doi.org/10.3109/0284186X.2015.1011757.

    Article  PubMed  Google Scholar 

  15. Feilchenfeldt J, Varga Z, Siano M, Grabsch HI, Held U, Schuknecht B, et al. Brain metastases in gastro-oesophageal adenocarcinoma: insights into the role of the human epidermal growth factor receptor 2 (HER2). Br J Cancer. 2015;113(5):716–21. https://doi.org/10.1038/bjc.2015.279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Howlader N, Altekruse SF, Li CI, Chen VW, Clarke CA, Ries LA, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014. https://doi.org/10.1093/jnci/dju055.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Limon D, Gal O, Gordon N, Katz L, Perl G, Purim O, et al. Brain metastasis in gastroesophageal adenocarcinoma and HER2 status. J Neurooncol. 2018;138(2):315–20. https://doi.org/10.1007/s11060-018-2798-4.

    Article  CAS  PubMed  Google Scholar 

  18. Hosonaga M, Saya H, Arima Y. Molecular and cellular mechanisms underlying brain metastasis of breast cancer. Cancer Metastasis Rev. 2020;39(3):711–20. https://doi.org/10.1007/s10555-020-09881-y.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lee-Hoeflich ST, Crocker L, Yao E, Pham T, Munroe X, Hoeflich KP, et al. A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res. 2008;68(14):5878–87. https://doi.org/10.1158/0008-5472.CAN-08-0380.

    Article  CAS  PubMed  Google Scholar 

  20. Blazquez R, Wlochowitz D, Wolff A, Seitz S, Wachter A, Perera-Bel J, et al. PI3K: A master regulator of brain metastasis-promoting macrophages/microglia. Glia. 2018;66(11):2438–55. https://doi.org/10.1002/glia.23485.

    Article  PubMed  Google Scholar 

  21. Tanner M, Hollmen M, Junttila TT, Kapanen AI, Tommola S, Soini Y, et al. Amplification of HER-2 in gastric carcinoma: association with topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol. 2005;16(2):273–8. https://doi.org/10.1093/annonc/mdi064.

    Article  CAS  PubMed  Google Scholar 

  22. Saeki H, Oki E, Kashiwada T, Arigami T, Makiyama A, Iwatsuki M, et al. Re-evaluation of HER2 status in patients with HER2-positive advanced or recurrent gastric cancer refractory to trastuzumab (KSCC1604). Eur J Cancer. 2018;105:41–9. https://doi.org/10.1016/j.ejca.2018.09.024.

    Article  CAS  PubMed  Google Scholar 

  23. Steeg PS, Camphausen KA, Smith QR. Brain metastases as preventive and therapeutic targets. Nat Rev Cancer. 2011;11(5):352–63. https://doi.org/10.1038/nrc3053.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kodack DP, Chung E, Yamashita H, Incio J, Duyverman AM, Song Y, et al. Combined targeting of HER2 and VEGFR2 for effective treatment of HER2-amplified breast cancer brain metastases. Proc Natl Acad Sci U S A. 2012;109(45):E3119–27. https://doi.org/10.1073/pnas.1216078109.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wolstenholme V, Hawkins M, Ashley S, Tait D, Ross G. HER2 significance and treatment outcomes after radiotherapy for brain metastases in breast cancer patients. Breast. 2008;17(6):661–5. https://doi.org/10.1016/j.breast.2008.04.006.

    Article  PubMed  Google Scholar 

  26. Tarantino P, Carmagnani Pestana R, Corti C, Modi S, Bardia A, Tolaney SM, et al. Antibody-drug conjugates: smart chemotherapy delivery across tumor histologies. CA Cancer J Clin. 2022;72(2):165–82. https://doi.org/10.3322/caac.21705.

    Article  PubMed  Google Scholar 

  27. Yoshida J, Sugiyama K, Satoh M, Shiraishi K, Nishibori R, Kitagawa C. Efficacy of trastuzumab deruxtecan in an advanced gastric cancer patient with brain metastasis. Curr Probl Cancer. 2021;45(6):100757. https://doi.org/10.1016/j.currproblcancer.2021.100757.

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank all the enrolled patients and their families. Role of funder statement The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.

Funding

This work was supported by grants from the National Natural Science Foundation of China (82073377,81772587 to MZ.Q., 82172748 to DJ.Y.), Natural Science Foundation of Guangdong (2021A1515012439 to MZ.Q.).

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Author notes

  1. Ming-Yu Lai, Wen-Long Guan and Jing Yang have contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China

    Ming-Yu Lai, Wen-Long Guan, Jing Yang, Yu-Ting Sun & Miao-Zhen Qiu

  2. Department of Pathology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China

    Shi-Xun Lu

  3. Department of Experiment Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China

    Li-Qiong Yang & Da-Jun Yang

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Contributions

QMZ, YDJ: design and conduct of the study. LMY, GWL, YJ: collection, management, analysis, and interpretation of the data. SYT, LSX and YLQ: investigation, methodology. LMY and GWL: resource, writing the original draft. All the authors reviewed and approved the manuscript. All the authors decided to submit the manuscript for publication.

Corresponding authors

Correspondence to Da-Jun Yang or Miao-Zhen Qiu.

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Competing interests

The authors declare no potential conflicts of interest.

Ethics approval and consent to participate

This study was performed in accordance with the Declaration of Helsinki protocols and was approved by the Ethics Committee from Sun Yat-sen University Cancer Center with accession N.O.: B2022-633-01. All authors had access to the study data and reviewed and approved the final manuscript.

Access to data and data analysis

Miao-Zhen Qiu and Da-Jun Yang had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Lai, MY., Guan, WL., Yang, J. et al. The relationship between brain metastasis and HER2 expression status in gastric cancer. Clin Transl Oncol 26, 765–773 (2024). https://doi.org/10.1007/s12094-023-03306-2

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