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 Content is derived from published guidelines and regulatory sources and may contain errors or outdated information.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 IVA
Single extrathoracic metastatic lesion or contralateral lung nodule or pleural/pericardial involvement. Metastatic but potentially oligometastatic.
4 test recommendations across 1 clinical indication
Stage IVA metastatic HER2+. HER2 retesting on metastatic biopsy recommended. Full molecular profiling.
Required — 2 tests
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 retesting on metastatic biopsy recommended — HER2 status may change (up to 15% discordance).
Specimen
Evidence
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
Recommended — 2 tests
PIK3CA Mutation Analysis
PIK3CA
Hotspot mutation analysis of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) identifying the 11 most common activating mutations (exon 9: E542K, E545A/D/G/K, Q546E/K; exon 20: H1047L/R/Y). PIK3CA mutations occur in ~40% of HR+/HER2− metastatic breast cancer. FDA-approved companion diagnostic (therascreen PIK3CA RGQ PCR Kit) for alpelisib (Piqray) + fulvestrant per SOLAR-1 trial. OncoKB Level 1.
Ordering Note
PIK3CA mutation relevant in HER2+ disease for second-line targeting after HER2-directed progression.
Specimen
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.
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 |
|---|---|---|---|---|---|---|
| HER2 IHC/FISH | Covered | Covered | Covered | Unknown | Unknown | Unknown |
| Comprehensive NGS | Covered | Covered | Covered | Prior Auth | Covered | Covered |
| BRCA1/2 Germline | Covered | Covered | Covered | Covered | 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.