HER2-low breast cancer (IHC 1+ OR IHC 2+ with non-amplified ISH) — ~50-55% of HER2-non-po...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-BREAST-HER2-LOW-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-BREAST`
Sources	`SRC-DESTINY-BREAST04-MODI-2022` `SRC-ESMO-BREAST-METASTATIC-2024` `SRC-NCCN-BREAST-2025`

Red Flag Origin

Definition	HER2-low breast cancer (IHC 1+ OR IHC 2+ with non-amplified ISH) — ~50-55% of HER2-non-positive breast cancers. T-DXd 2L+ approved in HR+ and TNBC HER2-low post-chemo (DESTINY-Breast04 — mPFS 9.9 vs 5.1 mo, OS 23.4 vs 16.8 mo).
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-BREAST-HR-POS-2L, ALGO-BREAST-TNBC-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "her2_status",
      "value": "low"
    },
    {
      "finding": "her2_ihc",
      "value": "1+"
    },
    {
      "finding": "her2_ihc_ish",
      "value": "IHC2+/ISH-"
    }
  ],
  "type": "biomarker"
}

Notes

Pathology challenge: IHC 1+ vs 0 has poor inter-observer reproducibility — guideline efforts ongoing (ASCO/CAP 2023 update). DESTINY-Breast06 data extends to HER2-ultralow (IHC ≥0 with membrane staining) post-endocrine progression in HR+. ILD class warning still applies. Sequence: in HR+ HER2-low post-CDK4/6i + ≥1 prior chemo, T-DXd precedes sacituzumab govitecan in most algorithms.

Used By

Algorithms

ALGO-BREAST-HR-POS-2L - ALGO-BREAST-HR-POS-2L
ALGO-BREAST-TNBC-2L - ALGO-BREAST-TNBC-2L

Red flag

RF-BREAST-HER2-ULTRALOW-CANDIDATE - HER2-ultralow breast cancer (IHC > 0 < 1+; faint/incomplete membrane staining ≤10% of tum...