Clinicopathological factors associated with HER2-positive gastric cancer: A meta-analysis

Abstract

Background: The treatment of patients with advanced gastric cancer remains a most challenging task in the clinical practice. Recently, targeted therapies have significantly impacted the treatment strategy for many common malignancies. The use of trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2; also known as ERBB2), plus chemotherapy proved to improve median overall survival in patients with advanced gastric cancer, compared with chemotherapy alone in Trastuzumab for Gastric Cancer (ToGA) trial. However, the prognostic value of HER2 status in gastric cancer remains controversial. Therefore, the aim of this study was to investigate the clinical pathology significance of HER2 overexpression in resectable gastric cancer for selecting the right patients with gastric cancer who may benefit from trastuzumab treatment.

Methods: Publications reported the clinicopathological factors associated with HER2 status in gastric cancer from 2012 to 2017 were collected. The literature databases, such as "Cochrane Library", "Sciencedirect", "Springer", "PubMed", "Embase", were extensively searched to retrieve the clinical studies of HER2 expression in gastric cancer. The major outcomes measures were odds ratios (ORs) and their 95% CIs. Statistical analysis was carried out by Revman software 5.3. The Newcastle-Ottawa scale was used to assess the quality of evidence.

Result: Fifteen studies met our inclusion criteria. This study demonstrated that the pooled OR for HER2 positivity was associated with being male (OR: 1.42; 95% CI: 1.23-1.64), well/moderately differentiated tumor (OR: 2.76; 95% CI: 1.72-4.45), and for intestinal-type tumor (OR: 0.31; 95% CI: 0.25-0.38). However, it had no correlation with depth of tumor (P = .07), venous invasion (P = .82), and lymphovascular invasion (P = .24).

Conclusion: HER2-positive expression was associated with male gender, intestinal type, and well/moderate cell differentiation. We recommend that those gastric cancer patients who may benefit from trastuzumab treatment should be subjected to targeted therapies. However, detecting HER2 status may contribute to the target therapy for gastric carcinoma using trastuzumab. This would be strengthened by further studies incorporating comorbidity data, and outcomes from centralized programs.

Figure 1

PRISMA flow chart of selection process to identify studies eligible for pooling.

Figure 2

Pooled analysis of OR for the association of HER2 overexpression with the gender.

Figure 3

Pooled analysis of OR for the association of HER2 overexpression with the Lauren type.

Figure 4

Pooled analysis of OR for the association of HER2 overexpression with the Grade.