Germline BRCA1 ou BRCA2 variante patogênica no câncer de mama HER2 negativo (HR+ ou TNBC)....

Visão determinística da entidade fonte YAML. A autoridade clínica permanece com os IDs de fonte citados e estado de assinatura do revisor.

ID	`RF-BREAST-BRCA-GERMLINE-ACTIONABLE`
Tipo	Sinal de alerta
Estado	reviewed 2026-04-27 \| pending_clinical_signoff
Doenças	`DIS-BREAST`
Fontes	`SRC-EMBRACA-LITTON-2018` `SRC-ESMO-BREAST-METASTATIC-2024` `SRC-NCCN-BREAST-2025` `SRC-OLYMPIAD-ROBSON-2017`

Origem da bandeira vermelha

Definição	Germline BRCA1 or BRCA2 pathogenic variant in HER2-negative breast cancer (HR+ or TNBC). Olaparib (OlympiAD — mPFS 7.0 vs 4.2 mo vs chemo) and talazoparib (EMBRACA — mPFS 8.6 vs 5.6 mo) are FDA-approved for metastatic gBRCA HER2-negative breast. Adjuvant olaparib (OlympiA) for high-risk HER2-negative gBRCA early breast.
Direcção clínica	intensificar
Categoria	high-risk-biology
Algoritmo de deslocamentos	ALGO-BREAST-HR-POS-2L, ALGO-BREAST-TNBC-2L

Lógica de Desencadeamento

{
  "any_of": [
    {
      "finding": "brca1_germline",
      "value": "pathogenic"
    },
    {
      "finding": "brca2_germline",
      "value": "pathogenic"
    },
    {
      "finding": "brca1_brca2_germline",
      "value": "positive"
    },
    {
      "finding": "brca1_brca2_pathogenic",
      "value": true
    },
    {
      "finding": "germline_brca_status",
      "value": "pathogenic"
    }
  ],
  "type": "biomarker"
}

Notas

Germline-only — somatic BRCA1/2 in breast lacks the same prospective RCT evidence (use HRD assay where pathway-altered status sought). Genetic counseling mandatory (cascade testing of first-degree relatives; risk-reducing salpingo-oophorectomy). PALB2 has analogous HRR-deficient biology — emerging data support PARPi but off-label. Toxicity: cytopenias (~grade 3 anemia 16-25%), MDS / AML <1.5% long-term. Test before starting any PARPi candidate (chemotherapy de-escalation argument: avoid platinum-based sensitizing regimens if PARPi readily available).

Usado por

Algoritmos

ALGO-BREAST-HR-POS-2L - ALGO-BREAST-HR-POS-2L
ALGO-BREAST-TNBC-2L - ALGO-BREAST-TNBC-2L

Capítulos do Manual

HB-BREAST-HER2-POS-MET-1L - Câncer de mama metastático HER2+: raciocínio de primeira linha
HB-BREAST-HR-POS-HER2-NEG-1L - Câncer de mama metastático HR+/HER2-: raciocínio de primeira linha

Perguntas do Manual

HQ-BREAST-HER2-POS-1L-003 - HQ-BREAST-HER2-POS-1L-003
HQ-BREAST-HR-POS-1L-003 - HQ-BREAST-HR-POS-1L-003

Sinal de alerta

RF-PAN-PALB2-PARPI-CANDIDATE - Germline PALB2 variante patogênica — Parceiro de recrutamento da BRCA2; LOF biallélico produz um...