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

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

ID	`RF-BREAST-HER2-ULTRALOW-CANDIDATE`
Type	Red flag
Status	reviewed 2026-04-29 \| pending_clinical_signoff
Diseases	`DIS-BREAST`
Sources	`SRC-ESMO-BREAST-METASTATIC-2024` `SRC-NCCN-BREAST-2025`

Red Flag Origin

Definition	HER2-ultralow breast cancer (IHC > 0 < 1+; faint/incomplete membrane staining ≤10% of tumor cells) — a sub-tier between IHC 0 and IHC 1+ not part of standard ASCO/CAP scoring. DESTINY-Breast06 (Bardia 2024 ASCO plenary) extended T-DXd benefit beyond HER2-low to HER2-ultralow HR+ metastatic breast post-endocrine + CDK4/6i, chemo-naive in the metastatic setting (HER2-low cohort mPFS 13.2 vs 8.1 mo, HR 0.62; HER2-ultralow exploratory n=153 mPFS 13.2 vs 8.3 mo, HR 0.78). FDA label expansion anticipated 2026 — candidate RF until pivotal-trial Source SRC-DESTINY-BREAST06-BARDIA-2024 ingested.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-BREAST-HR-POS-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "her2_status",
      "value": "ultralow"
    },
    {
      "finding": "her2_ihc",
      "value": "ultralow"
    },
    {
      "finding": "her2_ihc_ultralow",
      "value": true
    }
  ],
  "type": "biomarker"
}

Notes

Candidate RF — DESTINY-Breast06 trial-Source not yet ingested (SRC-DESTINY-BREAST06-BARDIA-2024 flagged in BIO-HER2-ULTRALOW notes). Pathology re-scoring required: ASCO/CAP 2018 / 2023 guideline does not formally distinguish ultralow from IHC 0; central pathology in DESTINY-Breast06 reported lower inter-observer kappa for ultralow than HER2-low. Practical consequence: rescore archival biopsy with ultralow criteria before T-DXd consideration. ILD class warning unchanged from HER2-low / HER2-positive T-DXd indications. Distinct from RF-BREAST-HER2-LOW-ACTIONABLE (which gates IHC 1+ or 2+/ISH-); this RF gates the new ultralow stratum exclusively. Priority 72 places it just below HER2-low (priority 70) so when both could theoretically fire, HER2-low wins. Promote to draft:false once trial-Source ingested and FDA approval confirmed (anticipated 2026).

Used By

Indications

IND-BREAST-TNBC-2L-SACITUZUMAB - IND-BREAST-TNBC-2L-SACITUZUMAB