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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.
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.
In plain words · PTEN is the brake on the PI3K growth pathway; when a tumour loses it the pathway runs unchecked, which is why PTEN loss now selects patients for the AKT inhibitor capivasertib.
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.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
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.
“PTEN protein Loss/Deficient”
FDA: List of FDA-Authorized Companion Diagnostic Devices| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| PTEN alteration (with PIK3CA and AKT1 as the qualifying set) | Capivasertib | HR-positive / HER2-negative breast cancer | FDA | label |
| PTEN deficiency in tumour tissue (IHC) | Capivasertib | Metastatic hormone-sensitive prostate cancer | FDA | label |
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| FoundationOne CDx | Foundation Medicine | Breast Cancer - Tissue | CapivasertibFulvestrant | P170019/S048 (11/16/2023) |
| VENTANA PTEN (SP218) RxDx Assay | Ventana Medical Systems (Roche Tissue Diagnostics) | Metastatic hormone-sensitive prostate cancer (mHSPC) - Tissue | Capivasertib | P250031 (06/12/2026) |
Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.
It is the prospective test of the PI3K and androgen receptor feedback hypothesis in men, and it shows both halves of the answer: the biomarker-selected population benefits, and the benefit is small enough that the toxicity has to be weighed honestly.
PAKT gives the trial-based prevalence of PI3K-pathway alteration in first-line metastatic TNBC (one in five) and the strongest signal for AKT inhibition in that subgroup; the phase 3 CAPItello-290 did not confirm it.
PTEN loss, the most common PI3K-pathway lesion in TNBC, may mark primary immunotherapy resistance, and TMB may add to PD-L1 in choosing who gets checkpoint blockade.
LOTUS and PAKT together made the PI3K/AKT/PTEN-altered subgroup the target population for AKT inhibitors in TNBC; the phase 3 IPATunity130 later failed to confirm it, which is why no AKT inhibitor is approved here.
It made PTEN a protein test rather than a genomic one in this disease, and the concordance between early and late biopsies is the practical point: the diagnostic block usually answers the question, so a fresh biopsy is not needed to make this call.
This is the reference frequency table for basal-like disease: it explains why PARP inhibitors and platinum, borrowed from ovarian cancer, work in TNBC, and why the PI3K pathway is broken by copy number rather than the hotspot mutations that drugs were designed against.
It is the reason every prostate PI3K or AKT trial gives the drug with abiraterone rather than alone, and the reason PTEN loss is used to select for those combinations rather than as a general prognostic marker.
Shares Tumor mutational burden and PTEN alterations as molecular correlates of response to PD-1/L1 blockade in metastatic triple-negative breast cancer, FoundationOne CDx / Liquid CDx, Metastatic triple-negative breast cancer, Triple-negative breast cancer (TNBC) and the tag biomarker.
Shares Capivasertib, Immunohistochemistry (IHC), Endometrial cancer, HR-positive / HER2-negative breast cancer and the tag biomarker.
Shares Immunohistochemistry (IHC), Metastatic triple-negative breast cancer, Triple-negative breast cancer (TNBC), HR-positive / HER2-negative breast cancer and the tag biomarker.
Shares Immunohistochemistry (IHC), Endometrial cancer, HR-positive / HER2-negative breast cancer and the tag biomarker.
Shares Immunohistochemistry (IHC), Triple-negative breast cancer (TNBC), HR-positive / HER2-negative breast cancer and the tag biomarker.
Shares Immunohistochemistry (IHC), Triple-negative breast cancer (TNBC), HR-positive / HER2-negative breast cancer and the tag biomarker.
Shares FoundationOne CDx / Liquid CDx, Metastatic castration-resistant prostate cancer, Endometrial cancer, Triple-negative breast cancer (TNBC) and the tag biomarker.
Shares FoundationOne CDx / Liquid CDx, Metastatic castration-resistant prostate cancer, Triple-negative breast cancer (TNBC), Prostate cancer and the tag biomarker.