AKT1 E17K activating mutation in HR+/HER2- metastatic breast cancer — ~3-6% prevalence. C...

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

ID	`RF-BREAST-AKT1-E17K-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-BREAST`
Sources	`SRC-CAPITELLO291-TURNER-2023` `SRC-ESMO-BREAST-METASTATIC-2024` `SRC-NCCN-BREAST-2025`

Red Flag Origin

Definition	AKT1 E17K activating mutation in HR+/HER2- metastatic breast cancer — ~3-6% prevalence. Capivasertib + fulvestrant (CAPItello-291) is FDA-approved for HR+/HER2- advanced breast harboring PIK3CA / AKT1 / PTEN alteration after progression on endocrine ± CDK4/6i.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-BREAST-HR-POS-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "akt1_e17k",
      "value": true
    },
    {
      "finding": "akt1_mutation",
      "value": "E17K"
    },
    {
      "finding": "akt1_status",
      "value": "E17K-positive"
    }
  ],
  "type": "biomarker"
}

Notes

AKT1 E17K is the dominant (>90%) AKT1 hotspot. Tested via tissue NGS or ctDNA. Capivasertib hyperglycemia rate lower than alpelisib. Toxicity: diarrhea (70%), rash (35%), hyperglycemia (~16%). Concurrent PIK3CA / AKT1 / PTEN testing recommended at first progression on AI ± CDK4/6i — any single alteration triggers pathway-targeted therapy.

Used By

Algorithms

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

Red flag

RF-BREAST-AKT1-E17K-CAPIVASERTIB-CANDIDATE - AKT1 E17K activating hotspot specifically positioning capivasertib + fulvestrant in HR+/H...