# HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target?

Source: https://onco.cc/key-papers/paper-galdy-her2-biliary-tract-meta-analysis-cancer-metastasis-rev-2017/  
OnCo record `paper-galdy-her2-biliary-tract-meta-analysis-cancer-metastasis-rev-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: gallbladder-evidence
- Journal: Cancer Metastasis Reviews
- Year: 2017
- DOI: 10.1007/s10555-016-9645-x
- Authors: Galdy S, Lamarca A, McNamara MG, et al.
- Findings: 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.
- What it means: 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.
- Caveats: Scoring criteria varied across studies; the 26.5 percent overall figure includes weak staining.; Gallbladder cancer is pooled with extrahepatic cholangiocarcinoma.

## Sources

- Cancer Metastasis Rev 2017: https://doi.org/10.1007/s10555-016-9645-x
- PubMed: https://pubmed.ncbi.nlm.nih.gov/27981460/

## Connected records

- cancers: [Biliary tract cancer (all types)](https://onco.cc/cancers/biliary-tract-cancer/), [Extrahepatic cholangiocarcinoma (perihilar and distal)](https://onco.cc/cancers/extrahepatic-cholangiocarcinoma/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/)
- targets: [HER2](https://onco.cc/targets/her2/)
- terms: [FISH / ISH (in situ hybridisation)](https://onco.cc/terms/fish/), [HER2-positive (IHC 3+ or ISH-amplified)](https://onco.cc/terms/her2-positive/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- people: [Angela Lamarca](https://onco.cc/people/angela-lamarca/), [Juan W. Valle](https://onco.cc/people/juan-valle/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/)
- journals: [Cancer metastasis reviews](https://onco.cc/journals/cancer-metastasis-reviews/)
- roadmaps: [Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials](https://onco.cc/roadmaps/gallbladder-cancer-roadmap/)
- ideas: [Reflex HER2 testing of every advanced gallbladder and extrahepatic biliary cancer](https://onco.cc/ideas/idea-gbc-reflex-her2-testing-advanced-biliary/), [Report gallbladder cancer as its own population in every biliary trial](https://onco.cc/ideas/idea-gbc-report-gallbladder-separately-in-biliary-trials/)

---
JSON: https://onco.cc/api/v1/entities/paper-galdy-her2-biliary-tract-meta-analysis-cancer-metastasis-rev-2017.json