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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 Content is derived from published guidelines and regulatory sources and may contain errors or outdated information.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 →

Breast Cancer · HR+/HER2− Breast Cancer

Stage Stage I

Tumor ≤4 cm, no nodal or distant metastasis (T1-T2a, N0, M0). Surgically resectable.

3 test recommendations across 1 clinical indication

At Diagnosis

All invasive HR+/HER2− breast cancer Stage I at diagnosis. HER2 testing required; gene expression profiling (Oncotype DX) indicated for pT1b-pT2 pN0.

Required 1 test

RequiredFDA Companion Dx

HER2 Testing (IHC + FISH)

HER2 IHC/FISH

LOINC 85319-2

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

Required for all invasive breast cancer regardless of stage to establish HER2 status.

Specimen

FFPE primary tumor tissueFFPE metastatic site

Recommended 1 test

Recommended

Oncotype DX Recurrence Score (21-Gene Assay)

Oncotype DX

LOINC 81504-3

Gene expression profiling assay measuring 21 genes to generate a Recurrence Score (RS 0–100) predicting 10-year distant recurrence risk and chemotherapy benefit in HR+/HER2− early breast cancer. Low RS (0–25, postmenopausal; 0–15, premenopausal): endocrine therapy only. High RS (≥26, postmenopausal; ≥16, premenopausal): adjuvant chemotherapy plus endocrine therapy. TAILORx (N Engl J Med 2018) and RxPONDER (N Engl J Med 2021) established evidence base. NCCN Category 1 for pT1b-pT2, pN0-N1a.

Ordering Note

For pT1b (>5 mm) through pT2 (≤5 cm), pN0. Recurrence Score guides adjuvant chemotherapy decision.

Specimen

FFPE primary tumor (≥25% tumor)

Optional 1 test

Optional

MammaPrint 70-Gene Signature

MammaPrint

LOINC 85504-0

Microarray-based 70-gene signature classifying early-stage breast cancer as low or high genomic risk. MINDACT trial demonstrated that patients with high clinical risk but low genomic risk can safely forgo chemotherapy. FDA-cleared for HR+/HER2−, node-negative or 1-3 node positive disease. Alternative to Oncotype DX; preferred in some European centers.

Ordering Note

Alternative to Oncotype DX. MINDACT trial data. Order one or the other, not both.

Specimen

FFPE primary tumorFresh/frozen tumor

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.

TestMedicare (CMS)UnitedHealthAnthem BCBSHumanaCignaAetna
HER2 IHC/FISHCoveredCoveredCoveredUnknownUnknownUnknown
Oncotype DXCoveredCoveredCoveredCoveredCoveredCovered

Coverage data last verified via automated policy research. Always confirm current policies with each payer.

Reference only. Testing guidance shown is derived from published clinical guidelines and regulatory sources. It does not constitute a clinical recommendation for any individual patient. Payer coverage information is a general summary and may not reflect current policy or individual benefit design. Full disclaimer

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.

HR+/HER2− Breast Cancer — Stage I | Breast Cancer | genoCDS | genoCDS