BTC Diagnostics

Advancing Diagnostic Certainty in Biliary Tract Cancers (BTC)

Ventana Pathology BMUltraPlus

Now FDA-approved in BTC

PATHWAY anti-HER2/neu (4B5)
Rabbit Monoclonal Primary Antibody

The need for targeted therapies

Innovative HER2 testing is elevating hope for patients with Biliary Tract Cancer (BTC) that has progressed after first-line therapy. There is a significant unmet need for targeted therapies that can potentially improve survival. 

5-year survival table

Approximately, 60%-70% of patients present with locally advanced or metastatic cancer at diagnosis and are ineligible for surgery1 

The median overall survival for patients is <12 months2

Why HER2 testing is important 

HER2 is an important target for identifying BTC patients that have progressed after first-line therapy who may benefit from ZIIHERA® (zanidatamab).


*Based on a meta-analysis of published data in BTC showed that among 38 studies (including 3839 patients that reported HER2 positivity assessed by IHC)

26.5% of patients with BTC have HER2 overexpression

HER2 positivity is key to determining eligibility for ZIIHERA® (zanidatamab)

Treatment with zanidatamab led to a median duration of response (DOR)  of 14.9 months (95% CI: 7.4-not estimable)  and a median overall survival (OS) of 18.1 (95% CI, 12.2-23.2) months in patients with IHC3+ tumors, and the 6- and 12-month OS rates were 90.1% (95% CI, 79.2%-95.4%) and 65.0% (95% CI, 51.6%-75.6%), respectively8

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Staining characteristics for biliary tract cancer

staining patterns

Staining strength

Weak to moderate to strong staining is counted toward total % tumor cell membrane staining (resection)*9

Cholangiocarcinoma Resection (4B5),3+ H&E, 20x
Cholangiocarcinoma Resection (4B5),3+ 4x
Cholangiocarcinoma Resection (4B5),3+ 10x
Cholangiocarcinoma Resection (4B5),3+ 20x

At 4x, membrane staining can be seen in >95% of tumor cells, consistent with IHC score of 3+
At 10x & 20x, homogeneous strong basolateral membrane staining in >95% of tumor cells

Cholanigocarcinoma Resection, 3+ (borderline with 2+) H&E, 20x
Cholanigocarcinoma Resection, 3+ (borderline with 2+) 4x
Cholanigocarcinoma Resection, 3+ (borderline with 2+) 10x
Cholanigocarcinoma Resection, 3+ (borderline with 2+) 20x

At 4x, membrane staining is seen in 15% of tumor cells, consistent with IHC score of 3+
At 10x & 20x, images demonstrate clearly resolved basolateral membrane staining consistent with 2+ staining

Staining strength tumor cell cluster

Weak to moderate to strong staining is counted toward total tumor cell cluster membrane staining (biopsy)*9

Gallbladder Adenocarcinoma Biopsy, 3+ H&E, 20x
Gallbladder Adenocarcinoma Biopsy, 3+ 4x
Gallbladder Adenocarcinoma Biopsy, 3+ 10x
Gallbladder Adenocarcinoma Biopsy, 3+ 20x

At 4x, membrane staining is easily visualized in >5 contiguous tumor cells, consistent with IHC score 3+
At 20x, homogeneous strong basolateral and circumferential membrane staining is seen
Accompanying weak to moderate cytoplasmic staining is also present, but does not obscure membrane staining

*Refer to the PATHWAY HER2/neu (4B5) Rabbit Monoclonal Primary Antibody Interpretation Guide for Biliary Tract Cancer for scoring/interpretation guidance 
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BTC Scoring Algorithm

PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody
staining icon
Staining
  • Lateral, basolateral and complete membrane staining all count towards IHC score
  • For 2+ score, include cells with membrane staining of weak to moderate intensity
scoring icon
Scoring
  • Scoring methods for biopsies and resections are the same but utilize different cut-points
  • Resection Specimens: >10% tumor cells with membranous staining
  • Biopsy Specimens: >5 contiguous tumor cells with membranous staining
decisions icon
Decisions
  • For decision making, 4x and 20x objectives are the most important

Decision making

For decision making, 4x and 20x objectives are the most important in Her2 scoring of BTC
Resection specimens objective/magnification method decision tree9
Resection Specimens
HER2 BTC Resection Flow
Biopsy specimens objective/magnification method flow diagram9
HER2 BTC Biopsy Specimen Flow

Find a HER2 for BTC testing site

Bilary tract testing with PATHWAY HER2 (4B5) is the latest expansion of Roche’s market-leading portfolio of IHC/ISH companion diagnostics designed to provide critical insights that enable more informed clinical decisions and diagnostic certainty in HER2 testing. 

Caris Life Sciences

4610 S 44th Pl.
Phoenix, AZ 85040
Sources
  1. Tella SH, et al. Lancet Oncol. 2020;21(1):e29–e41. 
  2. Mirallas O, et al. ESMO Open. 2022;7(3):100503.
  3. American Cancer Society, "Survival Rates for Bile Duct Cancer" - Accessed October 2024.
  4. American Cancer Society, "Survival Rates for Gallbladder Cancer" - Accessed October 2024.
  5. Kang MJ, et al. Sci Rep. 2022;12(1):10206.
  6. Koshiol J, et al. BMC Cancer. 2022;22(1):1178–1189. 6. Azizi AA, et. al. Crit Rev Oncol Hematol. 2021 Jul;163:103328. 
  7. Galdy, S, et al. Cancer and Metastasis Reviews. 2017;36:141-57. PMID: WOS:000399178000011
  8. Harding JJ, et al. Lancet Oncol. 2023: 24:772-82. Publication on phase 2b trial of zani in patients with HER-amplified BTC (HERIZON-BTC-01) 
  9. PATHWAY HER2/neu Rabbit Monoclonal Primary Antibody Interpretation Guide for Biliary Tract Cancer

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