HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target?
Pooling 40 studies, about one in five bile duct and gallbladder cancers outside the liver over-express HER2, against fewer than one in twenty inside the liver, which is why HER2 drugs matter most for gallbladder cancer.
Overview
Systematic review and meta-analysis from Manchester of HER2 and HER3 overexpression (immunohistochemistry) and amplification (in situ hybridisation) in biliary tract cancers; 40 of 440 screened studies qualified. Overall HER2 expression was 26.5 percent (95 percent CI 18.9 to 34.1). In 27 high-quality studies (moderate or strong staining), extrahepatic biliary cancers showed 19.9 percent (12.8 to 27.1) overexpression against 4.8 percent (0 to 14.5) for intrahepatic cholangiocarcinoma (p=0.0049). Amplification was 57.6 percent in patients selected by overexpression and 17.9 percent unselected. HER3 overexpression was 27.9 percent.
- HER2 overexpression 19.9 percent (95 percent CI 12.8 to 27.1) in extrahepatic biliary cancers vs 4.8 percent (0 to 14.5) in intrahepatic cholangiocarcinoma in high-quality studies.
- Amplification 57.6 percent among overexpressors vs 17.9 percent unselected.
- HER3 overexpression 27.9 percent.
The prevalence estimate that made HER2 the first gallbladder-relevant target; it argues for testing every advanced gallbladder cancer, since one in five may qualify for zanidatamab or trastuzumab deruxtecan.
- Scoring criteria varied across studies; the 26.5 percent overall figure includes weak staining.
- Gallbladder cancer is pooled with extrahepatic cholangiocarcinoma.
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