Medical Disclaimer
genoCDS is a clinical reference tool for qualified healthcare professionals only. Content is derived from published guidelines and regulatory sources and may contain errors or outdated information. It is not a substitute for professional medical judgment, institutional protocols, or individual patient assessment. Always verify recommendations against current primary sources before making clinical decisions. Full disclaimer →
Stage Stage IIA
Tumor >4–5 cm, no nodal or distant metastasis (T2b, N0, M0). Resectable.
4 test recommendations across 1 clinical indication
Stage IIA TNBC. PDL1 CPS and BRCA1/2 germline required at diagnosis per NCCN and KEYNOTE-522.
Required — 3 tests
PD-L1 Expression by Immunohistochemistry (IHC)
PD-L1 IHC
Measurement of PD-L1 (programmed death-ligand 1; CD274) protein expression on tumor cells by IHC. Reported as Tumor Proportion Score (TPS) for NSCLC. Key thresholds: TPS <1% (PD-L1 negative), TPS 1–49% (low expression), TPS ≥50% (high expression). FDA-approved companion diagnostics: 22C3 pharmDx (pembrolizumab), 28-8 pharmDx (nivolumab), SP142 (atezolizumab), SP263 (durvalumab). PD-L1 ≥50% qualifies for pembrolizumab monotherapy first-line; all TPS levels are relevant for combination chemo-immunotherapy selection.
Ordering Note
PD-L1 CPS (Combined Positive Score) ≥10 required for pembrolizumab eligibility in neoadjuvant TNBC per KEYNOTE-522. Use 22C3 antibody clone for breast cancer.
Specimen
Evidence
KEYNOTE-522: pembrolizumab + chemo significantly improved pCR and EFS in early TNBC regardless of PDL1 status, but PDL1 CPS guides metastatic use.
BRCA1/BRCA2 Germline Testing
BRCA1/2 Germline
Full sequence analysis and large rearrangement detection of BRCA1 and BRCA2 germline DNA in peripheral blood. Germline BRCA1/2 pathogenic variants found in ~5–7% of unselected breast cancer; up to 15–20% in TNBC. Eligibility criterion for PARP inhibitor therapy: olaparib (Lynparza, OLYMPIAD trial, FDA-approved 2018) and talazoparib (Talzenna, EMBRACA trial, FDA-approved 2018) for HER2− metastatic breast cancer. Also establishes hereditary risk for first-degree relatives. NCCN recommends germline testing for all metastatic breast cancer patients.
Ordering Note
Germline BRCA1/2 required in all high-risk TNBC at diagnosis. TNBC has 15-20% germline BRCA prevalence.
Specimen
Evidence
NCCN Category 1: germline BRCA1/2 for all high-risk TNBC at diagnosis.
HER2 Testing (IHC + FISH)
HER2 IHC/FISH
HER2 (ERBB2) status testing by immunohistochemistry (IHC) with reflex to FISH for IHC 2+ equivocal results, per ASCO/CAP 2018 guidelines. IHC 3+ = HER2 positive. FISH amplification ratio ≥2.0 or average HER2 copy number ≥6.0 signals/cell = HER2 positive. IHC 1+ and 2+/FISH non-amplified = HER2 low (eligible for T-DXd). Required for all newly diagnosed invasive breast cancer. FDA-approved companion diagnostic for multiple HER2-targeted therapies.
Ordering Note
HER2 required to confirm triple-negative status and identify HER2-low (IHC 1+) disease.
Specimen
Recommended — 1 test
Comprehensive Solid Tumor NGS Panel
Comprehensive NGS
Next-generation sequencing panel covering ≥300 cancer-relevant genes, including all major NSCLC drivers (EGFR, ALK, ROS1, BRAF, KRAS, MET, RET, NTRK, HER2, FGFR), plus tumor mutational burden (TMB) and microsatellite instability (MSI). Examples include FoundationOne CDx, Tempus xT, Caris MI Transcriptome, and equivalent institutional panels. Preferred over single-gene sequential testing for efficiency and cost-effectiveness.
Specimen
Payer Coverage
Payer Coverage Summary
Coverage status as of last policy review. Prior authorization requirements and coverage criteria may change. Verify directly with each payer before ordering.
| Test | Medicare (CMS) | UnitedHealth | Anthem BCBS | Humana | Cigna | Aetna |
|---|---|---|---|---|---|---|
| PD-L1 IHC | Covered | Covered | Covered | Covered | Covered | Covered |
| BRCA1/2 Germline | Covered | Covered | Covered | Covered | Covered | Covered |
| HER2 IHC/FISH | Covered | Covered | Covered | Unknown | Unknown | Unknown |
| Comprehensive NGS | Covered | Covered | Covered | Prior Auth | Covered | Covered |
Coverage data last verified via automated policy research. Always confirm current policies with each payer.
Recommendations on this page are derived from publicly available guidelines (NCCN, ASCO, ESMO, FDA, OncoKB) and are paraphrased for reference. They do not constitute medical advice. Evidence levels reflect the grading systems of each respective organization and should be interpreted in clinical context. This reference is updated periodically but may not reflect the most recent guideline revisions.