Triple-negative breast cancer (TNBC): estrogen receptor (ER) <1% nuclear staining on IHC...

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

ID	`RF-BREAST-TNBC`
Type	Red flag
Status	reviewed 2026-05-08 \| pending_clinical_signoff
Diseases	`DIS-BREAST`
Sources	`SRC-KEYNOTE-355-CORTES-2020` `SRC-KEYNOTE-522-SCHMID-2022` `SRC-NCCN-BREAST-2025`

Red Flag Origin

Definition	Triple-negative breast cancer (TNBC): estrogen receptor (ER) <1% nuclear staining on IHC AND progesterone receptor (PR) <1% nuclear staining on IHC AND HER2-negative (IHC 0 or 1+, OR IHC 2+ with ISH non-amplified). TNBC represents ~15-20% of all invasive breast cancers and is defined by the absence of all three hormone/growth-factor receptor targets. Clinical significance: TNBC lacks ER, PR, and HER2 targets, precluding endocrine therapy (tamoxifen, aromatase inhibitors) and HER2-directed therapy. Treatment is chemotherapy-based: - Early TNBC: pembrolizumab + neoadjuvant chemotherapy (KEYNOTE-522; Schmid NEJM 2022) — pCR rate 64.8% vs 51.2% with chemo alone, regardless of PD-L1 status. KEYNOTE-522 is the standard-of-care regimen. - Metastatic TNBC (BRCA-WT): pembrolizumab + chemotherapy (KEYNOTE-355) for CPS ≥10; chemotherapy alone (nab-paclitaxel, paclitaxel, or gemcitabine+carboplatin...
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-BREAST-1L

Trigger Logic

{
  "all_of": [
    {
      "any_of": [
        {
          "finding": "er_status",
          "value": "negative"
        },
        {
          "finding": "er_ihc",
          "value": "negative"
        },
        {
          "finding": "er_ihc",
          "value": "0%"
        },
        {
          "finding": "er_ihc",
          "value": "absent"
        },
        {
          "finding": "BIO-ESTROGEN-RECEPTOR",
          "value": "negative"
        }
      ]
    },
    {
      "any_of": [
        {
          "finding": "pr_status",
          "value": "negative"
        },
        {
          "finding": "pr_ihc",
          "value": "negative"
        },
        {
          "finding": "pr_ihc",
          "value": "0%"
        },
        {
          "finding": "pr_ihc",
          "value": "absent"
        },
        {
          "finding": "BIO-PROGESTERONE-RECEPTOR",
          "value": "negative"
        }
      ]
    },
    {
      "any_of": [
        {
          "finding": "her2_status",
          "value": "negative"
        },
        {
          "finding": "her2_ihc",
          "value": "0"
        },
        {
          "finding": "her2_ihc",
          "value": "1+"
        },
        {
          "finding": "her2_ish",
          "value": "non_amplified"
        }
      ]
    }
  ],
  "type": "receptor_status_composite"
}

Notes

W5c RF authoring. Converts free-text `{condition: "ER <1% AND PR <1% (TNBC)"}` in ALGO-BREAST-1L step 3 into a formal RF entity. The trigger uses an `all_of` composite with ER-negative, PR-negative, and HER2-negative conditions. Each receptor check uses an `any_of` to accommodate multiple finding key naming conventions (er_status, er_ihc, BIO-ESTROGEN-RECEPTOR). In ALGO-BREAST-1L sequential logic, step 1 first gates HER2+ via RF-BREAST-HER2-AMP-ACTIONABLE. Patients reaching step 3 are HER2-negative by definition. The HER2-negative component of this RF is included for standalone use but is not strictly required within the sequential algo. KEYNOTE-522 (Schmid NEJM 2022, PMID 35294803): early TNBC pembro+chemo — pCR 64.8% vs 51.2%, regardless of PD-L1; EFS benefit maintained at 5yr. KEYNOTE-355 (Cortes NEJM 2020, PMID 31789049): metastatic TNBC CPS ≥10 — pembro+chemo mPFS 9.7 vs 5.6 mo. ER/PR thresholds: ASCO/CAP 2020 guideline: ER or PR positive ≥1% nuclear staining. Values <1% are ER-negative or PR-negative respectively. This RF fires when BOTH ER and PR are below the 1% threshold. CHARTER §6.1: Two-reviewer clinical co-lead signoff required before removing draft: true.

Used By

Algorithms

ALGO-BREAST-1L - ALGO-BREAST-1L