# Reflex HER2 testing of every advanced gallbladder and extrahepatic biliary cancer

Source: https://onco.cc/ideas/idea-gbc-reflex-her2-testing-advanced-biliary/  
OnCo record `idea-gbc-reflex-her2-testing-advanced-biliary` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Between one in eleven and one in five gallbladder cancers is HER2-positive and two HER2 drugs are now approved, but testing still happens only when someone asks. Making it automatic on every advanced biliary diagnosis, on resection tissue where it exists, would find the patients the trials were built for.

## Summary

HER2 overexpression is about 20 percent in extrahepatic biliary cancers in the 2017 meta-analysis and 9.4 percent of gallbladder cancers by the HERIZON-BTC-01 definition in a 2026 resected series, which also found frequent heterogeneity involving under half of tumour cells, so small biopsies can miss it. Zanidatamab produced a 41.3 percent response rate in HER2-positive disease and trastuzumab deruxtecan has a tumour-agnostic HER2 3+ indication. Testing uptake in biliary cancer is not routinely audited. Reflex immunohistochemistry with in situ hybridisation for 2+ cases, ordered by pathology at diagnosis, is the model used for gastric and breast cancer.

## Fields

- Kind: Idea
- Last checked: 2026-09-24
- Tags: gallbladder-evidence
- Hypothesis: Pathology-initiated reflex HER2 testing at diagnosis of advanced gallbladder or extrahepatic biliary cancer will raise the tested fraction to above 90 percent and double the number of patients receiving HER2-directed therapy within two years.
- Rationale: The drugs exist and are approved; the bottleneck is a test that is cheap, standardised and already run in every pathology laboratory for other cancers.
- Proposed test: Before-and-after audit across a hepatobiliary network: proportion tested, turnaround time, HER2-positive rate, proportion of positives treated, with a heterogeneity sub-study comparing biopsy and resection specimens.
- Maturity: early-clinical
- Actor: clinic

## Sources

- Angerilli et al.: HER2 status and heterogeneity in 140 resected biliary cancers (Hum Pathol 2026): https://europepmc.org/article/MED/42595189
- HERIZON-BTC-01 (Lancet Oncol 2023): https://europepmc.org/article/MED/37276871

## Connected records

- cancers: [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/)
- drugs: [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/), [Zanidatamab](https://onco.cc/drugs/zanidatamab/)
- 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/)
- trials: [DESTINY-PanTumor02](https://onco.cc/trials/destiny-pantumor02/), [HERIZON-BTC-01](https://onco.cc/trials/herizon-btc-01/), [HERIZON-BTC-302](https://onco.cc/trials/herizon-btc-302/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Knowledge reaches practice too slowly](https://onco.cc/bottlenecks/b-knowledge-diffusion/)
- key papers: [HER2 status in extrahepatic cholangiocarcinoma and gallbladder carcinoma: Concordance between immunohistochemistry and chromogenic in situ hybridization in 140 Cases](https://onco.cc/key-papers/paper-angerilli-her2-gallbladder-extrahepatic-concordance-hum-pathol-2026/), [HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target?](https://onco.cc/key-papers/paper-galdy-her2-biliary-tract-meta-analysis-cancer-metastasis-rev-2017/), [Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study](https://onco.cc/key-papers/paper-harding-lancet-oncol/)
- 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/)

---
JSON: https://onco.cc/api/v1/entities/idea-gbc-reflex-her2-testing-advanced-biliary.json