HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH)
The tests that grade a breast or stomach cancer's HER2 level, from the original trastuzumab test in 1998 to the new 'HER2-low' and 'ultralow' cut-offs.
Overview
HercepTest (Dako, PMA P980018, 25 September 1998) was the first companion diagnostic ever approved, launched with trastuzumab. Roche's PATHWAY anti-HER2/neu (4B5) and INFORM HER2 Dual ISH are the other FDA-approved workhorses, extended to gastric cancer with the ToGA trial. The HER2-low era changed what a score means: in October 2022 the FDA approved PATHWAY 4B5 as the companion diagnostic for trastuzumab deruxtecan in HER2-low (IHC 1+ or 2+/ISH-negative) metastatic breast cancer after DESTINY-Breast04, and in January 2025 extended it to HER2-ultralow (IHC 0 with membrane staining) after DESTINY-Breast06. A score of 0 versus 1+ that once meant nothing now decides eligibility for an antibody-drug conjugate, which has forced pathologists to re-standardise the low end of the scale.
Approvals
| Region | Year | Indication |
|---|---|---|
| US | 1998 | HercepTest: HER2 overexpression to select trastuzumab in breast cancer (first companion diagnostic) |
| US | 2010 | HER2 testing extended to gastric and GEJ adenocarcinoma with trastuzumab (ToGA) |
| US | 2022 | PATHWAY 4B5 as companion diagnostic for trastuzumab deruxtecan in HER2-low breast cancer |
| US | 2025 | PATHWAY 4B5 extended to HER2-ultralow (IHC 0 with membrane staining) |
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Landmark trials in OnCo
Notes
top- What a result means: 3+ (or 2+ with amplification) is HER2-positive and unlocks trastuzumab-based therapy; 1+ or 2+ without amplification is HER2-low and, in metastatic disease, unlocks trastuzumab deruxtecan.
Latest papers
topQuery for this drug: (TITLE:"HER2 IHC and ISH companion assays" OR ABSTRACT:"HER2 IHC and ISH companion assays" OR TITLE:"HercepTest, PATHWAY 4B5, HER2 Dual ISH" OR ABSTRACT:"HercepTest, PATHWAY 4B5, HER2 Dual ISH" OR TITLE:"HercepTest" OR ABSTRACT:"HercepTest" OR TITLE:"PATHWAY anti-HER2" OR ABSTRACT:"PATHWAY anti-HER2" OR TITLE:"INFORM HER2 Dual ISH" OR ABSTRACT:"INFORM HER2 Dual ISH") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH), not a curated reading list.
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