{"entity":{"id":"pik3ca-hotspot-mutation","kind":"biomarker","name":"PIK3CA mutation","aka":["PIK3CA mutation","PIK3CA-mutated","PIK3CA H1047R","PIK3CA E545K","PIK3CA E542K","PIK3CA hotspot","PI3K mutation breast cancer"],"tldr":"PIK3CA mutations in the helical and kinase domains are found in about 40 percent of hormone-receptor-positive breast cancers. Alpelisib, inavolisib and capivasertib are approved for tumours that carry them.","summary":"Hotspots E542K and E545K (helical domain, exon 9) and H1047R (kinase domain, exon 20) are detected in tissue or plasma; the therascreen PIK3CA RGQ PCR Kit covers 11 mutations and FoundationOne CDx and Liquid CDx report the gene. Alpelisib (Piqray) is labelled with fulvestrant for HR-positive HER2-negative PIK3CA-mutated advanced breast cancer after endocrine therapy; inavolisib (Itovebi) with palbociclib and fulvestrant for endocrine-resistant PIK3CA-mutated disease recurring during or after adjuvant endocrine therapy; capivasertib (Truqap) with fulvestrant for tumours with PIK3CA, AKT1 or PTEN alterations. All three name an FDA-approved test. Hyperglycaemia and rash are the class effects that the PIK3CA result buys into.","asOf":"2026-09-23","links":[{"label":"PIQRAY prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b20b4e18-7a4b-4500-a08f-06c6dab0ee5b"},{"label":"Itovebi prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5de59f5b-e5db-410f-b692-658686ef4107"},{"label":"TRUQAP prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d698c106-2322-401e-b738-cbd83c843ecf"}],"tags":["biomarker","pi3k"],"related":["akt1-e17k","pten-alteration","esr1-mutation-ctdna"],"cancers":["breast-hr-positive","hr-positive-metastatic-post-cdk46","endometrial"],"sections":[],"technologies":[],"targets":[],"drugs":["alpelisib","inavolisib","capivasertib","therascreen-cdx","foundationone-cdx"],"companies":[],"institutions":[],"pathways":[],"terms":["hyperglycaemia","ngs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"pik3ca","measurement":"sequencing-variant","scoringRule":{"text":"A PIK3CA hotspot mutation (C420R, E542K, E545A/D/G/K, Q546E/R, H1047L/R/Y on the therascreen kit; wider sets on sequencing panels) in tumour tissue or plasma; a negative plasma result should be followed by tissue testing.","quote":"C420R, E542K, E545A, E545D [1635G>T only], E545G, E545K, Q546E, Q546R, H1047L, H1047R, and H1047Y","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools","sourceLabel":"FDA: List of FDA-Authorized Companion Diagnostic Devices"},"thresholds":[{"value":"PIK3CA-mutated","drugId":"alpelisib","cancerId":"breast-hr-positive","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b20b4e18-7a4b-4500-a08f-06c6dab0ee5b","quote":"PIQRAY is indicated in combination with fulvestrant for the treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen.","status":"current"},{"value":"PIK3CA-mutated, endocrine-resistant","drugId":"inavolisib","cancerId":"breast-hr-positive","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5de59f5b-e5db-410f-b692-658686ef4107","quote":"ITOVEBI, in combination with palbociclib and fulvestrant, is indicated for the treatment of adults with endocrine-resistant, PIK3CA -mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy","status":"current"},{"value":"PIK3CA, AKT1 or PTEN alteration","drugId":"capivasertib","cancerId":"breast-hr-positive","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d698c106-2322-401e-b738-cbd83c843ecf","quote":"in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN -alterations as detected by an FDA-approved test","status":"current"}],"tests":["foundationone-cdx","foundationone-liquid-cdx","guardant360-cdx","tempus-xt","caris-mi-cancer-seek"],"assays":["pik3ca-therascreen","foundationone-cdx-panel","foundationone-liquid-cdx"],"companionDiagnostics":[{"device":"therascreen PIK3CA RGQ PCR Kit","maker":"QIAGEN","companyId":"qiagen","drugs":["alpelisib"],"indication":"Breast Cancer - Tissue or Plasma","pma":"P190001 (05/24/2019) P190004 (05/24/2019)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"FoundationOne CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["alpelisib"],"indication":"Breast Cancer - Tissue","pma":"P170019/S006 (12/03/2019)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"FoundationOne Liquid CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["inavolisib"],"indication":"Breast Cancer - Plasma","pma":"P190032/S023 (10/10/2024)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"FoundationOne CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["capivasertib","fulvestrant"],"indication":"Breast Cancer - Tissue","pma":"P170019/S048 (11/16/2023)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"A PIK3CA mutation in hormone-receptor-positive breast cancer opens three targeted tablets given with fulvestrant: inavolisib (with palbociclib) if the cancer came back during or soon after adjuvant hormone therapy, and alpelisib or capivasertib after hormone therapy for advanced disease. All raise blood sugar, so your team will check glucose before and during treatment."},"route":"/biomarkers/pik3ca-hotspot-mutation/","neighbours":{"biomarker":[{"id":"akt1-e17k","kind":"biomarker","name":"AKT1 E17K mutation","route":"/biomarkers/akt1-e17k/"},{"id":"esr1-mutation-ctdna","kind":"biomarker","name":"ESR1 mutation (ligand-binding domain, usually in ctDNA)","route":"/biomarkers/esr1-mutation-ctdna/"},{"id":"pten-alteration","kind":"biomarker","name":"PTEN alteration (sequencing) and PTEN loss (IHC)","route":"/biomarkers/pten-alteration/"}],"cancer":[{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"hr-positive-metastatic-post-cdk46","kind":"cancer","name":"HR-positive metastatic breast cancer after CDK4/6 inhibitors","route":"/cancers/hr-positive-metastatic-post-cdk46/"}],"drug":[{"id":"alpelisib","kind":"drug","name":"Alpelisib","route":"/drugs/alpelisib/"},{"id":"capivasertib","kind":"drug","name":"Capivasertib","route":"/drugs/capivasertib/"},{"id":"foundationone-cdx","kind":"drug","name":"FoundationOne CDx / Liquid CDx","route":"/drugs/foundationone-cdx/"},{"id":"inavolisib","kind":"drug","name":"Inavolisib","route":"/drugs/inavolisib/"},{"id":"therascreen-cdx","kind":"drug","name":"therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF)","route":"/drugs/therascreen-cdx/"}],"term":[{"id":"hyperglycaemia","kind":"term","name":"Hyperglycaemia (PI3K/AKT inhibitor class effect)","route":"/terms/hyperglycaemia/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"}],"target":[{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"}]}}