HER3 Overexpression and Survival in Solid Tumors: a Meta-analysis

Background: The human epidermal growth factor receptor 3 (HER3) is an ErbB/HER family member that dimerizes with other ErbB receptors such as HER2. Numerous agents against HER3 are in clinical development despite variable data for the prognostic impact of HER3 expression. Here we report a meta-analysis of the association of HER3 expression and survival in solid tumors.

Methods: PubMed was searched for studies evaluating expression of HER3 (as measured by immunohistochemistry) and overall survival (OS) in solid tumors. Published data were extracted and computed into odds ratios (ORs) for death at 3 and 5 years. Data were pooled using the Mantel-Haenszel random-effect model. All statistical tests were two-sided.

Results: Analysis included 12 studies: three that evaluated colorectal cancer, two that evaluated gastric cancer, two that evaluated breast cancer, and one each that evaluated melanoma, ovarian cancer, head and neck cancer, pancreatic cancer, and cervical cancer. The median percentage of cancers with HER3 overexpression was 42.2%. HER3 was associated with worse OS at both 3 years (OR = 2.24, 95% confidence interval [CI] = 1.77 to 2.83, P < .001) and 5 years (OR = 2.20, 95% CI = 1.75 to 2.76, P < .001). Among studies with common HER2 overexpression (breast, gastric, and ovarian cancers), the magnitude of effect of HER3 on OS was statistically significantly greater for both 3-year OS (OR = 3.12, 95% CI = 2.24 to 4.37) and 5-year OS (OR = 2.84, 95% CI = 2.09 to 3.88).

Conclusions: Expression of HER3 is associated with worse survival in solid tumors. The influence of HER3 may be greater in those tumors where HER2 is commonly overexpressed.