HER2-low (breast — IHC 1+ OR IHC 2+ ISH-negative)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-HER2-LOW |
|---|---|
| Type | Biomarker |
| Aliases | ERBB2-lowHER2 IHC 1+HER2 IHC 2+/ISH-HER2-low (РМЗ — ІГХ 1+ АБО ІГХ 2+ ISH-)HER2-low breast |
| Status | reviewed 2026-04-29 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-DESTINY-BREAST04-MODI-2022 SRC-ESMO-BREAST-METASTATIC-2024 SRC-NCCN-BREAST-2025 |
Biomarker Facts
| Biomarker type | protein_expression_ihc |
|---|---|
| Measurement | MethodIHC (4B5 / HercepTest); reflex ISH (FISH/CISH/SISH) for IHC 2+. Breast scoring uses 2018 ASCO/CAP criteria — circumferential membranous staining ≥10%. UnitsIHC 0 | 1+ | 2+ (ISH-non-amplified) — HER2-low = IHC 1+ OR (IHC 2+ AND ISH HER2/CEP17 ratio <2.0 AND HER2 signals/cell <4.0) |
| Related biomarkers | BIO-HER2-SOLID BIO-ESTROGEN-RECEPTOR |
Notes
HER2-low (IHC 1+ OR IHC 2+/ISH-) covers ~50-55% of HER2-non-positive breast cancers. DESTINY-Breast04 (Modi 2022) established T-DXd efficacy 2L+ in HER2-low metastatic breast (HR+ post-endocrine + ≥1 prior chemo, OR TNBC post-≥1 prior chemo): mPFS 9.9 vs 5.1 mo, OS 23.4 vs 16.8 mo. DESTINY-Breast06 extended signal to HER2-ultralow (IHC ≥0 with membrane staining) post-endocrine in HR+. Pathology challenge: IHC 1+ vs 0 has poor inter-observer reproducibility — ASCO/CAP 2023 update ongoing. ILD class warning (~12% any-grade, 1-2% G≥3) is dominant safety concern. Distinct from BIO-HER2-SOLID (which is named/scoped for gastric/GEJ/CRC scoring conventions).
Used By
Actionability
BMA-HER2-LOW-BREAST- Trastuzumab deruxtecan (T-DXd, DS-8201) is FDA-approved (Aug 2022) for unresectable or me...
Biomarker
BIO-HER2-ULTRALOW- HER2-ultralow (breast — IHC > 0 < 1+; faint/incomplete membrane staining ≤10%)
Indications
IND-BREAST-HER2-LOW-2L-DATO-DXD- IND-BREAST-HER2-LOW-2L-DATO-DXD