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Erythroblastic oncogene B-2 status and intracranial metastatic disease in patients with gastrointestinal cancer: a systematic review

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Abstract

Purpose

The incidence of intracranial metastatic disease (IMD) in patients with gastrointestinal (GI) cancers is rising. Expression of the erythroblastic oncogene B-2 (ERBB2) is associated with an in increased risk of IMD in patients with breast cancer. The implications of ERBB2 expression for IMD risk in patients with GI cancers is less clear. The objective of this systematic review was to determine the incidence of IMD and OS in patients with ERBB2+ gastrointestinal cancers.

Methods

A literature search of MEDLINE, EMBASE, CENTRAL, and grey literature sources was conducted from date of database inception to July 2021. Included studies reported outcomes on patients with IMD secondary to ERBB2 GI cancers.

Results

Fourteen cohort studies met inclusion criteria, of which thirteen were retrospective. Eleven studies reported on gastric, esophageal, or gastroesophageal junction cancers. Three studies directly compared incidence of IMD based on ERBB2 status and among these, ERBB2+ patients had a higher incidence of IMD. One study indicated that ERBB2+ patients had significantly longer OS from the times of primary cancer (P = .015) and IMD diagnosis (P = .01), compared with patients with ERBB2− disease.

Conclusions

In this systematic review, patients with ERBB2+ GI cancer were more likely to develop IMD. Future study is required on the prognostic and predictive value of ERBB2 status in patients with GI cancers.

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Data availability

The data, analytic methods, and study materials will be made available to other researchers on request.

Abbreviations

ERBB2:

Erythroblastic oncogene B-2

GI:

Gastrointestinal

IMD:

Intracranial metastatic disease

OS:

Overall survival

References

  1. Arnold M et al (2020) Global burden of 5 major types of gastrointestinal cancer. Gastroenterology 159(1):335-349.e15. https://doi.org/10.1053/j.gastro.2020.02.068

    Article  Google Scholar 

  2. Schechter AL et al (1984) The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature 312(5994):513–516. https://doi.org/10.1038/312513A0

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  4. Da Silva AN, Nagayama K, Schlesinger DJ, Sheehan JP (2009) Gamma Knife surgery for brain metastases from gastrointestinal cancer: clinical article. J Neurosurg 111(3):423–430. https://doi.org/10.3171/2008.9.JNS08281

    Article  Google Scholar 

  5. Habbous S et al (2020) Incidence and real-world burden of brain metastases from solid tumors and hematologic malignancies in Ontario: a population-based study. Neuro-oncol Adv. https://doi.org/10.1093/NOAJNL/VDAA178

    Article  Google Scholar 

  6. Chamberlain RS, Nyberg C, Shrestha S (2015) “Gastrointestinal cancer and brain metastasis outcomes and management”, in brain metastases from primary tumors: epidemiology. Biol Ther. https://doi.org/10.1016/B978-0-12-801419-6.00015-X

    Article  Google Scholar 

  7. Palmieri D et al (2007) Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. Cancer Res 67(9):4190–4198. https://doi.org/10.1158/0008-5472.CAN-06-3316

    Article  CAS  Google Scholar 

  8. Pestalozzi BC et al (2006) Identifying breast cancer patients at risk for central nervous system (CNS) metastases in trials of the International breast cancer study group (IBCSG). Ann Oncol Off J Eur Soc Med Oncol 17(6):935–944. https://doi.org/10.1093/ANNONC/MDL064

    Article  CAS  Google Scholar 

  9. Pasquier D et al (2020) Treatment and outcomes in patients with central nervous system metastases from breast cancer in the real-life ESME MBC cohort. Eur J Cancer 125:22–30. https://doi.org/10.1016/J.EJCA.2019.11.001

    Article  Google Scholar 

  10. Howlader N et al (2014) US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. https://doi.org/10.1093/JNCI/DJU055

    Article  Google Scholar 

  11. Seung SJ, Traore AN, Pourmirza B, Fathers KE, Coombes M, Jerzak KJ (2020) A population-based analysis of breast cancer incidence and survival by subtype in ontario women. Curr Oncol 27(2):e191–e198. https://doi.org/10.3747/CO.27.5769

    Article  CAS  Google Scholar 

  12. Tsukada Y, Fouad A, Pickren JW, Lane WW (1983) central nervous system metastasis from breast carcinoma autopsy study. Cancer. https://doi.org/10.1002/1097-0142

    Article  Google Scholar 

  13. Lin NU, Bellon JR, Winer EP (2004) CNS metastases in breast cancer. J Clin Oncol 22(17):3608–3617. https://doi.org/10.1200/JCO.2004.01.175

    Article  Google Scholar 

  14. Darlix A et al (2018) Hormone receptors status: a strong determinant of the kinetics of brain metastases occurrence compared with HER2 status in breast cancer. J Neurooncol 138(2):369–382. https://doi.org/10.1007/S11060-018-2805-9/TABLES/3

    Article  CAS  Google Scholar 

  15. Gori S et al (2007) Central nervous system metastases in HER-2 positive metastatic breast cancer patients treated with trastuzumab: incidence, survival, and risk factors. Oncologist 12(7):766–773. https://doi.org/10.1634/THEONCOLOGIST.12-7-766

    Article  Google Scholar 

  16. Lin NU et al (2020) Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial. J Clin Oncol 38(23):2610. https://doi.org/10.1200/JCO.20.00775

    Article  CAS  Google Scholar 

  17. Brufsky AM et al (2011) Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res 17(14):4834–4843. https://doi.org/10.1158/1078-0432.CCR-10-2962

    Article  CAS  Google Scholar 

  18. Bang YJ et al (2010) 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. https://doi.org/10.1016/S0140-6736(10)61121-X

    Article  Google Scholar 

  19. Fusco N, Bosari S (2016) HER2 aberrations and heterogeneity in cancers of the digestive system: Implications for pathologists and gastroenterologists. World J Gastroenterol 22(35):7926–7937. https://doi.org/10.3748/wjg.v22.i35.7926

    Article  CAS  Google Scholar 

  20. Mitsui Y et al (2015) Trastuzumab in combination with docetaxel/cisplatin/S-1 (DCS) for patients with HER2-positive metastatic gastric cancer: feasibility and preliminary efficacy. Cancer Chemother Pharmacol. https://doi.org/10.1007/s00280-015-2807-7

    Article  Google Scholar 

  21. Siena S et al (2018) Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer. Ann Oncol 29(5):1108–1119. https://doi.org/10.1093/annonc/mdy100

    Article  CAS  Google Scholar 

  22. Gowryshankar A, Nagaraja V, Eslick GD (2014) HER2 status in Barrett’s esophagus & esophageal cancer: a meta analysis. J Gastrointest Oncol 5(1):25–35. https://doi.org/10.3978/j.issn.2078-6891.2013.039

    Article  Google Scholar 

  23. Lengyel CG et al (2020) Role of her-2 in gastrointestinal tumours beyond gastric cancer: a tool for precision medicine. Gastrointest Disord 3(1):1–22. https://doi.org/10.3390/gidisord3010001

    Article  Google Scholar 

  24. Ottawa Hospital Research Institute (2021) Newcastle Ottawa Scale: Coding Manual for Case-Control Studies

  25. University of Oxford (2020) The Centre for Evidence-Based Medicine

  26. Efstathiou J, Finkelstein SE (2018) The proceedings of the radiation oncology summit: ACRO 2018. J Radiat Oncol. https://doi.org/10.1007/s13566-018-0348-5

    Article  Google Scholar 

  27. Aprile G et al (2013) HER-2 Expression in brain metastases from colorectal cancer and corresponding primary tumors: a case cohort series. Int J Mol Sci 14(2):2370–2387. https://doi.org/10.3390/ijms14022370

    Article  CAS  Google Scholar 

  28. Blay C et al (2015) Incidence of brain metastases in HER2+ gastric or gastroesophageal junction adenocarcinoma. Acta Oncol. https://doi.org/10.3109/0284186X.2015.1011757

    Article  Google Scholar 

  29. Cavanna L et al (2018) Gastric cancer with brain metastasis and the role of human epidermal growth factor 2 status. Oncol Lett 15(4):5787–5791. https://doi.org/10.3892/ol.2018.8054

    Article  Google Scholar 

  30. Feilchenfeldt J et al (2015) Brain metastases in gastro-oesophageal adenocarcinoma: insights into the role of the human epidermal growth factor receptor 2 (HER2). Br J Cancer 113(5):716. https://doi.org/10.1038/BJC.2015.279

    Article  CAS  Google Scholar 

  31. Limon D et al (2018) Brain metastasis in gastroesophageal adenocarcinoma and HER2 status. J Neurooncol. https://doi.org/10.1007/s11060-018-2798-4

    Article  Google Scholar 

  32. Ma LX et al (2018) “Relationship between human epidermal growth factor receptor 2 (HER2) status and central nervous system metastases in gastroesophageal cancer. J Clin Oncol 36(suppl 4):145–145. https://doi.org/10.1200/JCO.2018.36.4_SUPPL.145

    Article  Google Scholar 

  33. Mitra D et al (2019) Enrichment of HER2 amplification in brain metastases from primary gastrointestinal malignancies. Oncologist. https://doi.org/10.1634/theoncologist.2018-0152

    Article  Google Scholar 

  34. Preusser M et al (2013) Brain metastases of gastro-oesophageal cancer: evaluation of molecules with relevance for targeted therapies. Anticancer Res 33(3):1065–1071

    Google Scholar 

  35. Safran H et al (2007) Phase I/II study of trastuzumab, paclitaxel, cisplatin and radiation for locally advanced, HER2 overexpressing, esophageal adenocarcinoma. Int J Radiat Oncol Biol Phys 67(2):405–409. https://doi.org/10.1016/J.IJROBP.2006.08.076

    Article  CAS  Google Scholar 

  36. Sperduto PW et al (2019) Estimating survival in patients with gastrointestinal cancers and brain metastases: an update of the graded prognostic assessment for gastrointestinal cancers (GI-GPA). Clin Transl Radiat Oncol. https://doi.org/10.1016/j.ctro.2019.06.007

    Article  Google Scholar 

  37. Tan RYC et al (2018) HER2 positive rates are enriched amongst colorectal cancer brain metastases: a study amongst 1920 consecutive patients. Ann Oncol Off J Eur Soc Med Oncol 29(7):1598–1599. https://doi.org/10.1093/annonc/mdy156

    Article  CAS  Google Scholar 

  38. Yoon HH et al (2016) Central nervous system relapse in patients with untreated HER2-positive esophageal or gastroesophageal junction adenocarcinoma. Int J Cancer. https://doi.org/10.1002/ijc.30200

    Article  Google Scholar 

  39. Tosi F et al (2020) Long-term clinical outcome of trastuzumab and lapatinib for her2-positive metastatic colorectal cancer. Clin Colorectal Cancer. https://doi.org/10.1016/j.clcc.2020.06.009

    Article  Google Scholar 

  40. Sperduto PW et al (2019) Survival and prognostic factors in patients with gastrointestinal cancers and brain metastases: have we made progress? Transl Res 208:63–72. https://doi.org/10.1016/j.trsl.2019.02.011

    Article  Google Scholar 

  41. A. G. et al (2013) HER-2 expression in brain metastases from colorectal cancer and corresponding primary tumors: a case cohort series. Int J Mol Sci 14(2):2370–2387

    Article  Google Scholar 

  42. Tosi F et al (2020) Long-term clinical outcome of trastuzumab and lapatinib for her2-positive metastatic colorectal cancer. Clin Colorectal Cancer 19(4):256-262.e2. https://doi.org/10.1016/j.clcc.2020.06.009

    Article  Google Scholar 

  43. Zimmer AS, Van Swearingen AED, Anders CK (2020) “HER2-positive breast cancer brain metastasis: a new and exciting landscape.” Cancer Reports. Wiley Ltd, Hoboken, p e1274

    Google Scholar 

  44. Wang S et al (2017) Brain metastases from hepatocellular carcinoma: Recent advances and future avenues. Oncotarget 8(15):25814–25829. https://doi.org/10.18632/oncotarget.15730

    Article  Google Scholar 

  45. Wu SG, Zhang WW, Sun JY, Li FY, Lin Q, He ZY (2018) Patterns of distant metastasis between histological types in esophageal cancer. Front Oncol. https://doi.org/10.3389/fonc.2018.00302

    Article  Google Scholar 

  46. Cavanna L et al (2018) Gastric cancer with brain metastasis and the role of human epidermal growth factor 2 status. Oncol Lett. https://doi.org/10.3892/ol.2018.8054

    Article  Google Scholar 

  47. Lemke J et al (2014) Brain Metastases in gastrointestinal cancers: Is there a role for surgery? Int J Mol Sci. https://doi.org/10.3390/ijms150916816

    Article  Google Scholar 

  48. Sperduto PW et al (2019) Survival and prognostic factors in patients with gastrointestinal cancers and brain metastases: have we made progress? Transl Res. https://doi.org/10.1016/j.trsl.2019.02.011

    Article  Google Scholar 

  49. Je Y, S. J, A. JA, W. DM, and G. ZL, (1999) Gastric cancer and metastasis to the brain. Ann Surg Oncol 6(8):771–776. https://doi.org/10.1007/S10434-999-0771-3

    Article  Google Scholar 

  50. Jørgensen JT, Hersom M (2012) HER2 as a prognostic marker in gastric cancer—a systematic analysis of data from the literature. J Cancer 3(1):137–144. https://doi.org/10.7150/jca.4090

    Article  Google Scholar 

  51. Erickson AW, Habbous S, Wright F, Lofters AK, Jerzak KJ, Das S (2021) Assessing the association of targeted therapy and intracranial metastatic disease. JAMA Oncol 7(8):1220–1224. https://doi.org/10.1001/JAMAONCOL.2021.1600

    Article  Google Scholar 

  52. Erickson AW et al (2020) HER2-targeted therapy prolongs survival in patients with HER2-positive breast cancer and intracranial metastatic disease: a systematic review and meta-analysis. Neuro-oncology Adv. https://doi.org/10.1093/NOAJNL/VDAA136

    Article  Google Scholar 

  53. Liu Q, Tong X, Wang J (2019) Management of brain metastases: history and the present. Chin Neurosurg J 5(1):1–8. https://doi.org/10.1186/S41016-018-0149-0/METRICS

    Article  Google Scholar 

  54. Fox BD, Cheung VJ, Patel AJ, Suki D, Rao G (2011) Epidemiology of metastatic brain tumors. Neurosurg Clin N Am 22(1):1–6. https://doi.org/10.1016/J.NEC.2010.08.007

    Article  Google Scholar 

  55. Siena S et al (2021) Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. Lancet Oncol 22(6):779–789. https://doi.org/10.1016/S1470-2045(21)00086-3

    Article  CAS  Google Scholar 

  56. Karan C et al (2022) Human epidermal growth factor receptor 2-targeting approaches for colorectal cancer: clinical implications of novel treatments and future therapeutic avenues. JCO Oncol Pract. https://doi.org/10.1200/OP.21.00904

    Article  Google Scholar 

  57. Strickler JH et al (2021) “MOUNTAINEER-02: Phase II/III study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma—trial in Progress.” J Clin oncol. https://doi.org/10.1200/JCO.2021.39.3_SUPPL.TPS252

    Article  Google Scholar 

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Funding

This study was supported by philanthropic funds from Gratitude 10.

Author information

Authors and Affiliations

  1. University of Waterloo, 200 University Ave W, Waterloo, ON, N2L 3G1, Canada

    Madison Sherman

  2. Institute of Medical Science, Faculty of Medicine, University of Toronto, 1 King’s College Circle, Toronto, ON, M5S 3K1, Canada

    Karolina Gaebe, Alyssa Y. Li & Sunit Das

  3. Division of Endocrinology, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada

    Karolina Gaebe

  4. Ontario Health (Cancer Care Ontario), Toronto, ON, Canada

    Steven Habbous & Sunit Das

  5. Epidemiology & Biostatistics, Western University, London, ON, Canada

    Steven Habbous

  6. Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Arjun Sahgal

  7. Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Arjun Sahgal & Michael J. Raphael

  8. Division of Medical Oncology and Hematology, Department of Medicine, University of Toronto, Toronto, ON, Canada

    Michael J. Raphael & Sunit Das

  9. Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, 1 King’s College Circle, Toronto, ON, M5S 1A8, Canada

    Anders W. Erickson

  10. Division of Neurosurgery, St. Michael’s Hospital, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada

    Sunit Das

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  1. Madison Sherman
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Contributions

MS, KG, AWE and SD contributed to the study conception and design. Material preparation and data collection were performed by MS and KG. Data analysis and interpretation were completed by MS, KG, AWE and SD. The first draft of the manuscript was written by MSh and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Sunit Das.

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Sherman, M., Gaebe, K., Li, A.Y. et al. Erythroblastic oncogene B-2 status and intracranial metastatic disease in patients with gastrointestinal cancer: a systematic review. J Neurooncol 160, 735–742 (2022). https://doi.org/10.1007/s11060-022-04195-1

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