PIK3CA hotspot activating mutation (E542K, E545K, H1047R/L) in HR+/HER2- metastatic breas...

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

ID	`RF-BREAST-PIK3CA-MUT-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` `SRC-SOLAR1-ANDRE-2019`

Red Flag Origin

Definition	PIK3CA hotspot activating mutation (E542K, E545K, H1047R/L) in HR+/HER2- metastatic breast cancer — present in ~40% of cases. After progression on endocrine ± CDK4/6i, alpelisib + fulvestrant (SOLAR-1 — mPFS 11.0 vs 5.7 mo) or capivasertib + fulvestrant (CAPItello-291 — mPFS 7.3 vs 3.1 mo) are 2L+ targeted options.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-BREAST-HR-POS-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "pik3ca_mutation",
      "value": true
    },
    {
      "finding": "pik3ca_status",
      "value": "mutated"
    },
    {
      "finding": "pik3ca_hotspot",
      "value": "positive"
    }
  ],
  "type": "biomarker"
}

Notes

Hyperglycemia + diarrhea + rash class on-target effects; DM screening + glycemic management plan required before alpelisib initiation. Capivasertib has a more favorable hyperglycemia profile but similar rash + diarrhea. Test on tumor tissue OR plasma ctDNA at progression (concordance high). Order AKT1 + PTEN concurrently — same drug class responds across all three pathway alterations (CAPItello-291 cohort).

Used By

Algorithms

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

Red flag

RF-BREAST-PIK3CA-COALT-INAVOLISIB-CANDIDATE - PIK3CA-mutant HR+/HER2- metastatic breast with co-alteration profile (endocrine-resistant...