HER2-ultralow (breast — IHC > 0 < 1+; faint/incomplete membrane staining ≤10%)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-HER2-ULTRALOW |
|---|---|
| Type | Biomarker |
| Aliases | ERBB2-ultralowHER2 0 with membrane stainingHER2 IHC >0 <1+HER2-ultralow (РМЗ — ІГХ > 0 < 1+; слабке/неповне мембранне забарвлення ≤10%)HER2-ultralow breast |
| Status | reviewed 2026-04-29 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-CIVIC SRC-ESMO-BREAST-METASTATIC-2024 SRC-NCCN-BREAST-2025 |
Biomarker Facts
| Biomarker type | protein_expression_ihc |
|---|---|
| Measurement | MethodIHC (4B5 / HercepTest) — HER2-ultralow defined operationally as IHC > 0 but < 1+: faint / barely perceptible incomplete membrane staining in ≤10% of tumor cells (DESTINY-Breast06 enrollment criterion). This sub-category sits between IHC 0 (absent) and IHC 1+ (faint complete membrane staining > 10%). Pathology reproducibility is poor — central review variability documented in DESTINY-Breast06. UnitsIHC ultralow | 0 | 1+ | 2+ | 3+ (HER2-ultralow excludes 0, 1+, 2+, 3+) |
| Related biomarkers | BIO-HER2-LOW BIO-HER2-SOLID BIO-ESTROGEN-RECEPTOR |
Notes
HER2-ultralow extends the HER2 expression spectrum below IHC 1+. DESTINY- Breast06 (ASCO 2024 plenary; Bardia et al.) randomized HR+ HER2-low or HER2-ultralow metastatic breast post-endocrine + CDK4/6i (chemo-naive in metastatic setting) to T-DXd vs investigator-choice chemotherapy. Primary PFS endpoint met in HER2-low cohort (mPFS 13.2 vs 8.1 mo, HR 0.62, p<0.0001); HER2-ultralow exploratory cohort (n=153) showed consistent benefit (mPFS 13.2 vs 8.3 mo, HR 0.78). FDA approval anticipated 2026 expanding T-DXd label below HER2-low. Pathology challenge dominant: IHC 0 vs ultralow is not part of standard ASCO/CAP scoring guideline (2018 / 2023 update); DESTINY-Breast06 used central pathology review and reported inter-observer kappa lower for ultralow than for HER2-low. Practical consequence: routine pathology reports today rarely distinguish ultralow from 0 — re-review of biopsy with ultralow scoring criteria required before T-DXd consideration. ILD class warning unchanged from HER2-low / HER2-positive T-DXd indications. Trial-Source SRC-DESTINY-BREAST06-BARDIA- 2024 not yet ingested — flag for ingestion chunk.
Used By
Actionability
BMA-HER2-LOW-BREAST- Trastuzumab deruxtecan (T-DXd, DS-8201) is FDA-approved (Aug 2022) for unresectable or me...
Red flag
RF-BREAST-HER2-ULTRALOW-CANDIDATE- HER2-ultralow breast cancer (IHC > 0 < 1+; faint/incomplete membrane staining ≤10% of tum...