{"entity":{"id":"pten-alteration","kind":"biomarker","name":"PTEN alteration (sequencing) and PTEN loss (IHC)","aka":["PTEN loss","PTEN deficiency","PTEN-deficient","PTEN alteration","PTEN deletion","PTEN mutation","PTEN IHC loss","PTEN null"],"tldr":"PTEN can be lost by mutation or deletion (read by sequencing) or as absent protein on a stain. Both readouts select capivasertib: alterations in breast cancer, and protein deficiency in metastatic hormone-sensitive prostate cancer.","summary":"PTEN loss removes the brake on PI3K signalling. In breast cancer capivasertib with fulvestrant is labelled for tumours with PIK3CA, AKT1 or PTEN alterations by FoundationOne CDx (CAPItello-291); in prostate cancer, following CAPItello-281, the 2026 label adds capivasertib with abiraterone for metastatic androgen pathway modulation-naive or -sensitive prostate cancer selected on PTEN deficiency in tumour tissue by the VENTANA PTEN (SP218) RxDx Assay (P250031, 12 June 2026). The IHC rule is loss of PTEN staining in tumour cells with retained stromal staining; the sequencing rule is a deleterious mutation or homozygous deletion.","asOf":"2026-09-23","links":[{"label":"TRUQAP prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d698c106-2322-401e-b738-cbd83c843ecf"}],"tags":["biomarker","pi3k"],"related":["pik3ca-hotspot-mutation","akt1-e17k"],"cancers":["breast-hr-positive","prostate-mhspc","prostate","endometrial","glioblastoma","tnbc","tnbc-metastatic","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["capivasertib","abiraterone","foundationone-cdx"],"companies":[],"institutions":[],"pathways":[],"terms":["pten-loss","ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020","paper-kim-lotus-ipatasertib-tnbc-lancet-oncol-2017","paper-tcga-breast-molecular-portraits-nature-2012","paper-ferraldeschi-pten-protein-loss-abiraterone-eur-urol-2015","paper-ipatential150-ipatasertib-abiraterone-pten-lancet-2021","paper-carver-pi3k-ar-reciprocal-feedback-prostate-cancer-cell-2011"],"journals":[],"dependsOn":[],"notes":["Triple-negative breast cancer: PTEN mutation or loss in up to 35% of basal-like tumours (Cancer Genome Atlas 2012) and 29% of 62 metastatic TNBC patients on immunotherapy, where it marked non-response (6% versus 48%) and shorter survival (Barroso-Sousa 2020); PTEN-low by immunohistochemistry was the co-primary population of LOTUS (Kim 2017). No approval in TNBC uses it.","Prostate cancer: deep deletion in 12 to 41% depending on disease state, 17.4% of 489 TCGA primaries and 25.7 to 41.0% in the metastatic castration-resistant cohorts (cBioPortal), with inactivating mutation adding 3 to 11% on top.","Protein loss is the measurement that matters and it is read by immunohistochemistry: loss in 40% of 144 men treated with abiraterone, associated with shorter overall survival, 14 against 21 months, hazard ratio 1.75, and concordant between hormone-sensitive and castration-resistant biopsies in 86% of 41 paired cases, so the diagnostic block usually answers the question (Ferraldeschi 2015).","It selects a treatment. IPATential150 prospectively stratified 1,101 men by PTEN loss on a single validated assay, found 521, 47%, PTEN-loss, and showed radiographic progression-free survival of 18.5 against 16.5 months with ipatasertib added to abiraterone in that group, hazard ratio 0.77, with grade 3 or higher adverse events in 70% against 39% (Sweeney 2021). The rationale is the reciprocal feedback between the PI3K and androgen receptor pathways (Carver 2011)."],"target":"pten","measurement":"sequencing-variant","scoringRule":{"text":"Sequencing: a deleterious PTEN mutation or deletion in tumour tissue or plasma. Immunohistochemistry: absence of PTEN staining in tumour cells with retained staining in adjacent stroma, on the VENTANA PTEN (SP218) RxDx Assay for prostate cancer.","quote":"PTEN protein Loss/Deficient","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":"PTEN alteration (with PIK3CA and AKT1 as the qualifying set)","drugId":"capivasertib","cancerId":"breast-hr-positive","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d698c106-2322-401e-b738-cbd83c843ecf","quote":"with one or more PIK3CA/AKT1/PTEN -alterations as detected by an FDA-approved test","status":"current"},{"value":"PTEN deficiency in tumour tissue (IHC)","drugId":"capivasertib","cancerId":"prostate-mhspc","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d698c106-2322-401e-b738-cbd83c843ecf","quote":"Select patients for the treatment of metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer with TRUQAP based on PTEN deficiency in tumor tissue","status":"current"}],"tests":["foundationone-cdx","foundationone-liquid-cdx","tempus-xt","caris-mi-profile"],"assays":["foundationone-cdx-panel"],"companionDiagnostics":[{"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"},{"device":"VENTANA PTEN (SP218) RxDx Assay","maker":"Ventana Medical Systems (Roche Tissue Diagnostics)","drugs":["capivasertib"],"indication":"Metastatic hormone-sensitive prostate cancer (mHSPC) - Tissue","pma":"P250031 (06/12/2026)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"PTEN loss means the PI3K growth pathway is running without its brake. In hormone-receptor-positive breast cancer it qualifies you for capivasertib with fulvestrant after hormone therapy; in newly metastatic hormone-sensitive prostate cancer a PTEN-deficient stain qualifies you for capivasertib added to abiraterone. Ask which test was used, because the breast indication uses sequencing and the prostate one a stain."},"route":"/biomarkers/pten-alteration/","neighbours":{"biomarker":[{"id":"akt1-e17k","kind":"biomarker","name":"AKT1 E17K mutation","route":"/biomarkers/akt1-e17k/"},{"id":"pik3ca-hotspot-mutation","kind":"biomarker","name":"PIK3CA mutation","route":"/biomarkers/pik3ca-hotspot-mutation/"}],"cancer":[{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate-mhspc","kind":"cancer","name":"Metastatic hormone-sensitive prostate cancer","route":"/cancers/prostate-mhspc/"},{"id":"tnbc-metastatic","kind":"cancer","name":"Metastatic triple-negative breast cancer","route":"/cancers/tnbc-metastatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"drug":[{"id":"abiraterone","kind":"drug","name":"Abiraterone acetate","route":"/drugs/abiraterone/"},{"id":"capivasertib","kind":"drug","name":"Capivasertib","route":"/drugs/capivasertib/"},{"id":"foundationone-cdx","kind":"drug","name":"FoundationOne CDx / Liquid CDx","route":"/drugs/foundationone-cdx/"}],"term":[{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"},{"id":"pten-loss","kind":"term","name":"PTEN loss","route":"/terms/pten-loss/"}],"paper":[{"id":"paper-schmid-pakt-capivasertib-tnbc-jco-2020","kind":"paper","name":"Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial","route":"/key-papers/paper-schmid-pakt-capivasertib-tnbc-jco-2020/"},{"id":"paper-tcga-breast-molecular-portraits-nature-2012","kind":"paper","name":"Comprehensive molecular portraits of human breast tumours","route":"/key-papers/paper-tcga-breast-molecular-portraits-nature-2012/"},{"id":"paper-kim-lotus-ipatasertib-tnbc-lancet-oncol-2017","kind":"paper","name":"Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial","route":"/key-papers/paper-kim-lotus-ipatasertib-tnbc-lancet-oncol-2017/"},{"id":"paper-ipatential150-ipatasertib-abiraterone-pten-lancet-2021","kind":"paper","name":"IPATential150: ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer","route":"/key-papers/paper-ipatential150-ipatasertib-abiraterone-pten-lancet-2021/"},{"id":"paper-ferraldeschi-pten-protein-loss-abiraterone-eur-urol-2015","kind":"paper","name":"PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate","route":"/key-papers/paper-ferraldeschi-pten-protein-loss-abiraterone-eur-urol-2015/"},{"id":"paper-carver-pi3k-ar-reciprocal-feedback-prostate-cancer-cell-2011","kind":"paper","name":"Reciprocal feedback regulation of PI3K and androgen receptor signalling in PTEN-deficient prostate cancer","route":"/key-papers/paper-carver-pi3k-ar-reciprocal-feedback-prostate-cancer-cell-2011/"},{"id":"paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020","kind":"paper","name":"Tumor mutational burden and PTEN alterations as molecular correlates of response to PD-1/L1 blockade in metastatic triple-negative breast cancer","route":"/key-papers/paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020/"}],"target":[{"id":"pten","kind":"target","name":"PTEN","route":"/targets/pten/"}]}}