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Published in: Journal of Neuro-Oncology 2/2018

01-06-2018 | Clinical Study

Brain metastasis in gastroesophageal adenocarcinoma and HER2 status

Authors: Dror Limon, Omer Gal, Noa Gordon, Lior Katz, Gali Perl, Ofer Purim, Limor Amit, Salomon M. Stemmer, Yulia Kundel, Irit Ben-Aharon, Baruch Brenner, Tali Siegal, Shlomit Yust-Katz

Published in: Journal of Neuro-Oncology | Issue 2/2018

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Abstract

The increased survival of patients with gastroesophageal adenocarcinoma (GAD) following improvements in treatment has been accompanied by a rising incidence of secondary brain metastasis. HER2 amplification/overexpression, which has been associated with an increased risk of brain metastasis in breast cancer, is found in about 20% of patients with GAD. The aim of this study was to evaluate the effect of HER2 status on brain metastasis in GAD. The database of a tertiary cancer center was searched for patients with GAD diagnosed in 2011–2015, and data were collected on clinical characteristics, brain metastasis, HER2 status, and outcome. We identified 404 patients with a confirmed diagnosis of GAD. HER2 results were available for 298: 69 (23.2%) positive and 227 negative. Brain metastasis developed in 15 patients with GAD (3.7%); HER2 results, available in 13, were positive in 6, negative in 6, and equivocal in 1. The brain metastasis rate was significantly higher in HER2-positive than HER2-negative patients with GAD (6/69, 8.7% vs. 6/227, 2.6%; RR = 3.3, 95% CI 1.1–9.9, p = 0.034). Median overall survival from diagnosis of brain metastasis was 2.3 months, with no significant difference by HER2 status. HER2 positive GAD patients may be at increased risk to develop BM. Clinicians should maintain a lower threshold for performing brain imaging in patients with HER2-positive GAD given their increased risk of brain metastasis. The role of anti-HER2 agents in the development and treatment of brain metastasis in GAD warrants further study.
Literature
2.
go back to reference Go PH et al (2011) Gastrointestinal cancer and brain metastasis: a rare and ominous sign. Cancer 117(16):3630–3640CrossRefPubMed Go PH et al (2011) Gastrointestinal cancer and brain metastasis: a rare and ominous sign. Cancer 117(16):3630–3640CrossRefPubMed
3.
go back to reference Wadhwa R et al (2013) Incidence of brain metastases after trimodality therapy in patients with esophageal or gastroesophageal cancer: implications for screening and surveillance. Oncology 85(4):204–207CrossRefPubMed Wadhwa R et al (2013) Incidence of brain metastases after trimodality therapy in patients with esophageal or gastroesophageal cancer: implications for screening and surveillance. Oncology 85(4):204–207CrossRefPubMed
4.
go back to reference Edwards BK et al (2014) Annual Report to the Nation on the status of cancer, 1975–2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer 120(9):1290–314CrossRefPubMed Edwards BK et al (2014) Annual Report to the Nation on the status of cancer, 1975–2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer 120(9):1290–314CrossRefPubMed
7.
go back to reference Tabouret E et al (2012) Recent trends in epidemiology of brain metastases: an overview. Anticancer Res 32(11):4655–4662PubMed Tabouret E et al (2012) Recent trends in epidemiology of brain metastases: an overview. Anticancer Res 32(11):4655–4662PubMed
8.
go back to reference Altaha R et al (2005) Increased risk of brain metastases in patients with HER-2/neu-positive breast carcinoma. Cancer 103(3):442–443CrossRefPubMed Altaha R et al (2005) Increased risk of brain metastases in patients with HER-2/neu-positive breast carcinoma. Cancer 103(3):442–443CrossRefPubMed
9.
go back to reference Gaedcke J et al (2007) Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer. Mod Pathol 20(8):864–870CrossRefPubMed Gaedcke J et al (2007) Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer. Mod Pathol 20(8):864–870CrossRefPubMed
10.
go back to reference Janjigian YY et al (2012) Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis. Ann Oncol 23(10):2656–2662CrossRefPubMed Janjigian YY et al (2012) Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis. Ann Oncol 23(10):2656–2662CrossRefPubMed
11.
go back to reference Van Cutsem E et al (2015) HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer 18(3):476–484CrossRefPubMed Van Cutsem E et al (2015) HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer 18(3):476–484CrossRefPubMed
12.
go back to reference Chua TC, Merrett ND (2012) Clinicopathologic factors associated with HER2-positive gastric cancer and its impact on survival outcomes: a systematic review. Int J Cancer 130(12):2845–2856CrossRefPubMed Chua TC, Merrett ND (2012) Clinicopathologic factors associated with HER2-positive gastric cancer and its impact on survival outcomes: a systematic review. Int J Cancer 130(12):2845–2856CrossRefPubMed
13.
go back to reference 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 376(9742):687–697CrossRefPubMed 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 376(9742):687–697CrossRefPubMed
14.
go back to reference Blay C et al (2015) Incidence of brain metastases in HER2 + gastric or gastroesophageal junction adenocarcinoma. Acta Oncol 54(10):1833–1835CrossRefPubMed Blay C et al (2015) Incidence of brain metastases in HER2 + gastric or gastroesophageal junction adenocarcinoma. Acta Oncol 54(10):1833–1835CrossRefPubMed
15.
go back to reference 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(12):1747CrossRefPubMedCentralPubMed 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(12):1747CrossRefPubMedCentralPubMed
16.
go back to reference Yoon HH et al (2016) Central nervous system relapse in patients with untreated HER2-positive esophageal or gastroesophageal junction adenocarcinoma. Int J Cancer 139(7):1626–1631CrossRefPubMed Yoon HH et al (2016) Central nervous system relapse in patients with untreated HER2-positive esophageal or gastroesophageal junction adenocarcinoma. Int J Cancer 139(7):1626–1631CrossRefPubMed
17.
go back to reference Mirza A et al (2014) Investigation of the epithelial to mesenchymal transition markers S100A4, vimentin and Snail1 in gastroesophageal junction tumors. Dis Esophagus 27(5):485–492CrossRefPubMed Mirza A et al (2014) Investigation of the epithelial to mesenchymal transition markers S100A4, vimentin and Snail1 in gastroesophageal junction tumors. Dis Esophagus 27(5):485–492CrossRefPubMed
18.
go back to reference Fisher OM et al (2017) The prognostic value of TP53 mutations in oesophageal adenocarcinoma: a systematic review and meta-analysis. Gut 66(3):399–410CrossRefPubMed Fisher OM et al (2017) The prognostic value of TP53 mutations in oesophageal adenocarcinoma: a systematic review and meta-analysis. Gut 66(3):399–410CrossRefPubMed
19.
go back to reference Chiam K et al (2015) Circulating serum exosomal miRNAs as potential biomarkers for esophageal adenocarcinoma. J Gastrointest Surg 19(7):1208–1215CrossRefPubMed Chiam K et al (2015) Circulating serum exosomal miRNAs as potential biomarkers for esophageal adenocarcinoma. J Gastrointest Surg 19(7):1208–1215CrossRefPubMed
20.
go back to reference Ren JL et al (2017) C-Met as a potential novel prognostic marker in squamous cell carcinoma and adenocarcinoma of esophagus: evidence from a meta-analysis. Panminerva Med 59(1):97–106PubMed Ren JL et al (2017) C-Met as a potential novel prognostic marker in squamous cell carcinoma and adenocarcinoma of esophagus: evidence from a meta-analysis. Panminerva Med 59(1):97–106PubMed
21.
go back to reference Koo T, Kim IA (2016) Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment. Radiat Oncol J 34(1):1–9CrossRefPubMedCentralPubMed Koo T, Kim IA (2016) Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment. Radiat Oncol J 34(1):1–9CrossRefPubMedCentralPubMed
22.
go back to reference Palmieri D et al (2007) Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. Cancer Res 67(9):4190–4198CrossRefPubMed Palmieri D et al (2007) Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. Cancer Res 67(9):4190–4198CrossRefPubMed
23.
go back to reference Le Scodan R et al (2011) Brain metastases from breast cancer: prognostic significance of HER-2 overexpression, effect of trastuzumab and cause of death. BMC Cancer 11:395CrossRefPubMedCentralPubMed Le Scodan R et al (2011) Brain metastases from breast cancer: prognostic significance of HER-2 overexpression, effect of trastuzumab and cause of death. BMC Cancer 11:395CrossRefPubMedCentralPubMed
24.
go back to reference Park IH et al (2009) Trastuzumab treatment beyond brain progression in HER2-positive metastatic breast cancer. Ann Oncol 20(1):56–62CrossRefPubMed Park IH et al (2009) Trastuzumab treatment beyond brain progression in HER2-positive metastatic breast cancer. Ann Oncol 20(1):56–62CrossRefPubMed
25.
go back to reference Krop IE et al (2015) Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA. Ann Oncol 26(1):113–119CrossRefPubMed Krop IE et al (2015) Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA. Ann Oncol 26(1):113–119CrossRefPubMed
26.
go back to reference Shen Q et al (2015) Breast cancer with brain metastases: clinicopathologic features, survival, and paired biomarker analysis. Oncologist 20(5):466–473CrossRefPubMedCentralPubMed Shen Q et al (2015) Breast cancer with brain metastases: clinicopathologic features, survival, and paired biomarker analysis. Oncologist 20(5):466–473CrossRefPubMedCentralPubMed
27.
go back to reference Priedigkeit N et al (2016) Intrinsic subtype switching and acquired ERBB2/HER2 amplifications and mutations in breast cancer brain metastases. JAMA Oncol 3:666–671CrossRef Priedigkeit N et al (2016) Intrinsic subtype switching and acquired ERBB2/HER2 amplifications and mutations in breast cancer brain metastases. JAMA Oncol 3:666–671CrossRef
28.
go back to reference Amato M et al (2017) HER2 status in gastric cancer: comparison between primary and distant metastatic disease. Pathol Oncol Res 23(1):55–61CrossRefPubMed Amato M et al (2017) HER2 status in gastric cancer: comparison between primary and distant metastatic disease. Pathol Oncol Res 23(1):55–61CrossRefPubMed
29.
go back to reference Kraszkiewicz M, Wydmanski J (2015) Brain metastases from stomach cancer: the role of different treatment modalities and efficacy of palliative radiotherapy. Rep Pract Oncol Radiother 20(1):32–37CrossRefPubMed Kraszkiewicz M, Wydmanski J (2015) Brain metastases from stomach cancer: the role of different treatment modalities and efficacy of palliative radiotherapy. Rep Pract Oncol Radiother 20(1):32–37CrossRefPubMed
30.
Metadata
Title
Brain metastasis in gastroesophageal adenocarcinoma and HER2 status
Authors
Dror Limon
Omer Gal
Noa Gordon
Lior Katz
Gali Perl
Ofer Purim
Limor Amit
Salomon M. Stemmer
Yulia Kundel
Irit Ben-Aharon
Baruch Brenner
Tali Siegal
Shlomit Yust-Katz
Publication date
01-06-2018
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 2/2018
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-018-2798-4

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