CHEK2 germline pathogenic (e.g. 1100delC) confers ~2× breast-cancer risk; no PARPi activi...

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

ID	`BMA-CHEK2-GERMLINE-BREAST`
Type	Actionability
Status	reviewed 2026-04-27 \| pending_clinical_signoff \| actionability review required
Diseases	`DIS-BREAST`
Sources	`SRC-ESMO-BREAST-METASTATIC-2024` `SRC-NCCN-BREAST-2025`

Actionability Facts

Biomarker	`BIO-HRR-PANEL`
Variant	CHEK2 germline pathogenic
Disease	`DIS-BREAST`
ESCAT tier	IIA
Recommended combinations	standard breast therapy by subtype, enhanced screening (annual MRI from age 40)
Contraindicated monotherapy	PARPi monotherapy (no demonstrated benefit)
Evidence summary	CHEK2 germline pathogenic (e.g. 1100delC) confers ~2× breast-cancer risk; no PARPi activity demonstrated (TBCRC-048 CHEK2 cohort minimal response). Standard HR/HER2-directed therapy. ESCAT IIA (predisposition) / OncoKB Level 3A.

Notes

Cascade testing per NCCN. CHEK2 c.1100delC (Eastern European founder) is the most common pathogenic variant. Bilateral mastectomy not routinely recommended (risk lower than BRCA).

Used By

No reverse references found in the YAML corpus.