Published online Aug 6, 2019. doi: 10.12998/wjcc.v7.i15.1964
Peer-review started: April 15, 2019
First decision: May 16, 2019
Revised: June 16, 2019
Accepted: June 26, 2019
Article in press: June 27, 2019
Published online: August 6, 2019
The clinical significance of intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity is unclear for HER2-positive gastric cancer, although it has been reported to be a significant prognosticator for HER2-positive breast cancer, which has received trastuzumab-based chemotherapy.
To clarify the clinical significance of intratumoral HER2 heterogeneity for HER2-positive gastric cancer, which has received trastuzumab-based chemotherapy.
Patients with HER2-positive unresectable or metastatic gastric cancer who received trastuzumab-based chemotherapy as a first line treatment were included. The patients were classified into two groups according to their intratumoral HER2 heterogeneity status examined by immunohistochemistry (IHC) on endoscopic biopsy specimens before treatment, and their clinical response to chemotherapy and survival were compared.
A total of 88 patients were included in this study, and HER2 heterogeneity was observed in 23 (26%) patients (Hetero group). The overall response rate was significantly better in patients without HER2 heterogeneity (Homo group) (Homo vs Hetero: 79.5% vs 35.7%, P = 0.002). Progression-free survival of trastuzumab-based chemotherapy was significantly better in the Homo group (median, 7.9 vs 2.5 mo, HR: 1.905, 95%CI: 1.109-3.268). Overall survival was also significantly better in the Homo group (median survival time, 25.7 vs 12.5 mo, HR: 2.430, 95%CI: 1.389-4.273). Multivariate analysis revealed IHC HER2 heterogeneity as one of the independent poor prognostic factors (HR: 3.115, 95%CI: 1.610-6.024).
IHC of HER2 heterogeneity is the pivotal predictor for trastuzumab-based chemotherapy. Thus, HER2 heterogeneity should be considered during the assessment of HER2 expression.
Core tip: Although intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity has been reported as an important predictor of trastuzumab-based chemotherapy for HER2-positive breast cancer, the clinical significance of HER2 heterogeneity for gastric cancer had been unclear. We defined intratumoral HER2 heterogeneity as biopsy specimens were taken from two or more different portions of the tumor that showed different HER2 positivity by immunohistochemistry, and HER2 heterogeneity based on this definition was a pivotal poor predictor of tumor shrinkage and poor prognosticator. Thus, intratumoral HER2 heterogeneity should be included in the assessment of HER2 positivity.