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Germline BRCA1/2 mutation (gBRCAm) breast cancer (HER2-negative, ~5-10% of metastatic): o...

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

IDBMA-HRD-STATUS-BREAST
TypeActionability
Statusreviewed 2026-04-27 | pending_clinical_signoff | actionability review required
DiseasesDIS-BREAST
SourcesSRC-CIVIC SRC-ESMO-BREAST-EARLY-2024 SRC-ESMO-BREAST-METASTATIC-2024 SRC-NCCN-BREAST-2025

Actionability Facts

BiomarkerBIO-HRD-STATUS
Variantgermline BRCA1/2 (gBRCA) — primary FDA companion biomarker; somatic BRCA1/2 also actionable; broader HRD-genomic signatures investigational
DiseaseDIS-BREAST
ESCAT tierIA
Recommended combinationsolaparib monotherapy (gBRCAm HER2-negative metastatic per SRC-NCCN-BREAST-2025, SRC-ESMO-BREAST-METASTATIC-2024), talazoparib monotherapy (gBRCAm HER2-negative metastatic per SRC-NCCN-BREAST-2025), olaparib 1y adjuvant (gBRCAm high-risk early breast post-(neo)adjuvant chemo per SRC-NCCN-BREAST-2025, SRC-ESMO-BREAST-EARLY-2024)
Evidence summaryGermline BRCA1/2 mutation (gBRCAm) breast cancer (HER2-negative, ~5-10% of metastatic): olaparib monotherapy is FDA-approved 2L+ for gBRCAm HER2-negative metastatic breast cancer based on OlympiAD (Robson NEJM 2017 — mPFS 7.0 vs 4.2 mo, HR 0.58); talazoparib monotherapy is FDA-approved on similar criteria (EMBRACA Litton NEJM 2018 — mPFS 8.6 vs 5.6 mo, HR 0.54) per SRC-NCCN-BREAST-2025, SRC-ESMO-BREAST-METASTATIC-2024. In the adjuvant setting, olaparib for 1y is FDA-approved for gBRCAm HER2-negative high-risk early breast cancer based on OlympiA (Tutt NEJM 2021 — IDFS HR 0.58, OS HR 0.68) per SRC-NCCN-BREAST-2025, SRC-ESMO-BREAST-EARLY-2024.

Notes

ESCAT IA / OncoKB Level 1 (gBRCAm). Somatic BRCA mutations and broader HRD-genomic signatures (Myriad MyChoice CDx) have less consistent evidence in breast — current FDA-companion is BRACAnalysis CDx for gBRCAm. ESMO 2024 advanced breast guidelines flag PARP-i is preferred 2L over CDK4/6 sequencing in gBRCAm/HR+ metastatic when available. Source-gap: SRC-OLYMPIA, SRC-OLYMPIAD, SRC-EMBRACA not yet ingested.

Used By

No reverse references found in the YAML corpus.