1. Definition:
- IHC (Immunohistochemistry) detects HER2 protein expression on the cell membrane of tumor cells.
- IHC 3+ = HER2 overexpression, which qualifies the tumor as HER2-positive for therapy.
2. Scoring Criteria (per ASCO/CAP 2025 guidelines for breast cancer):
| IHC Score | Membrane Staining | Interpretation |
|---|---|---|
| 0 | No staining or <10% of tumor cells | Negative |
| 1+ | Faint/barely perceptible in >10% of tumor cells; incomplete membrane staining | Negative |
| 2+ | Weak/moderate complete membrane staining in >10% OR circumferential incomplete staining | Equivocal → requires ISH/FISH confirmation |
| 3+ | Uniform, intense, circumferential membrane staining in >10% of tumor cells | Positive → HER2-targeted therapy indicated |
Key points for pharmacists:
- 3+ = unequivocally HER2-positive → patient can receive trastuzumab, pertuzumab, ADCs, or TKIs.
- Predictive, not prognostic: IHC 3+ predicts response to HER2-targeted therapies, not necessarily aggressive disease alone.
- Must ensure test performed on invasive tumor, not DCIS or metastasis only (unless metastatic biopsy is available).
- Re-testing may be needed if metastatic tumor subtype differs from primary.
3. Practical interpretation:
- IHC 3+: “HER2 overexpressed → eligible for HER2-targeted therapy”
- IHC 0–1+: HER2-negative → standard HER2 therapy not indicated
- IHC 2+: Equivocal → must confirm gene amplification by FISH/ISH
Example for context:
- Trastuzumab is effective only in IHC 3+ or FISH-amplified tumors, not in IHC 0–1+.
- Toxicities (cardiotoxicity, infusion reactions) are only relevant if HER2-targeted therapy is used.