You are here
Extra-gain of HER2-positive cases through HER2 reassessment in primary and metastatic sites in advanced gastric cancer with initially HER2-negative primary tumours: Results of GASTric cancer HER2 reassessment study 1 (GASTHER1)
European Journal of Cancer, January 2016, Pages 42 - 50
The intratumoural heterogeneity of human epidermal growth factor receptor 2 (HER2) expression in gastric cancer is a major challenge when identifying patients who might benefit from HER2-targeting therapy. We investigated the significance of re-evaluation of HER2 status in primary sites and metastatic or recurrent sites in advanced gastric cancer patients whose primary tumours were initially HER2-negative.
Patients and methods
In part I of this study, we evaluated the significance of repeat endoscopic biopsy in unresectable or metastatic gastric cancer patients whose tumours were initially HER2-negative. In part II, we examined the HER2 positivity rate in metastatic or recurrent sites in patients whose primary tumours were HER2-negative in biopsy or surgical specimens.
In part I (n = 183), we identified patients with HER2-positive tumours for a rescued HER2 positivity rate of 8.7% (95% confidence interval [CI], 4.6–12.8%) that was associated with tumour location (diffuse stomach versus other = 0% versus 11.7%, P = 0.013), Bormann type (IV versus others = 0% versus 11.7%, P = 0.013), and initial biopsy HER2 immunohistochemistry score (0 versus 1 versus 2 = 6.7% versus 15.4% versus 25.0%, P = 0.028). Part II (n = 175) resulted in HER2 positivity of 5.7% (95% CI 2.3–9.1%) that was significantly associated with metastatic site (liver versus others = 17.2% versus 3.4%, P = 0.012). When compared with a historical control that showed HER2 positivity on initial assessment, patients who had rescued HER2 positivity had similar treatment benefits from trastuzumab-containing first-line chemotherapy.
Repeat HER2 assessment in primary and metastatic or recurrent sites is recommended in patients with advanced gastric cancer whose primary tumour is initially HER2-negative.
- The intratumoural heterogeneity of human epidermal growth factor receptor 2 (HER2) status is a major challenge.
- We reassess HER2 in primary and metastatic sites in initially HER2(–) gastric cancer.
- Reassessment finds 8.7% (primary sites) and 5.7% (metastatic sites) HER2(+) disease.
- Patients with rescued HER2(+) have benefits from trastuzumab-containing therapy.
- We find significant clinical factors associated with rescued HER2 positivity.
Keywords: HER2, Gastric cancer, Intratumoural heterogeneity, Primary lesion, Metastatic lesion, Conversion, Reassessment.
a Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
b Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
c Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
∗ Corresponding author: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Republic of Korea. Tel.: +82 2 3010 3230; fax: +82 2 3010 8772.
1 The first three authors contributed equally to this work.
© 2015 Elsevier Ltd, All rights reserved.