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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.
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.
In plain words · PIK3CA is the most commonly mutated gene in hormone-driven breast cancer. Drugs against it work, but hitting it cleanly without raising blood sugar took years.
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.
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.
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.
“C420R, E542K, E545A, E545D [1635G>T only], E545G, E545K, Q546E, Q546R, H1047L, H1047R, and H1047Y”
FDA: List of FDA-Authorized Companion Diagnostic Devices| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| PIK3CA-mutated | Alpelisib | HR-positive / HER2-negative breast cancer | FDA | label |
| PIK3CA-mutated, endocrine-resistant | Inavolisib | HR-positive / HER2-negative breast cancer | FDA | label |
| PIK3CA, AKT1 or PTEN alteration | Capivasertib | HR-positive / HER2-negative breast cancer | FDA | label |
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| therascreen PIK3CA RGQ PCR Kit | QIAGEN | Breast Cancer - Tissue or Plasma | Alpelisib | P190001 (05/24/2019) P190004 (05/24/2019) |
| FoundationOne CDx | Foundation Medicine | Breast Cancer - Tissue | Alpelisib | P170019/S006 (12/03/2019) |
| FoundationOne Liquid CDx | Foundation Medicine | Breast Cancer - Plasma | Inavolisib | P190032/S023 (10/10/2024) |
| FoundationOne CDx | Foundation Medicine | Breast Cancer - Tissue | CapivasertibFulvestrant | P170019/S048 (11/16/2023) |
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.
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.
This is the sourced bridge between expression subtype and mutation: it tells a clinician that a LAR tumour is the one to sequence for PIK3CA and AKT1, and that immunomodulatory biology is a favourable prognostic group before any immunotherapy.
Shares ESR1 mutation (ligand-binding domain, usually in ctDNA), Alpelisib, Capivasertib, HR-positive metastatic breast cancer after CDK4/6 inhibitors and the tag biomarker.
Shares PTEN alteration (sequencing) and PTEN loss (IHC), Inavolisib, Alpelisib, Capivasertib.
Shares therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF), FoundationOne CDx / Liquid CDx, Next-generation sequencing (NGS), Non-small-cell lung cancer and the tag biomarker.
Shares FoundationOne CDx / Liquid CDx, Next-generation sequencing (NGS), Non-small-cell lung cancer and the tag biomarker.
Shares FoundationOne CDx / Liquid CDx, Next-generation sequencing (NGS), Triple-negative breast cancer (TNBC), Colorectal cancer and the tag biomarker.
Shares therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF), Next-generation sequencing (NGS), Colorectal cancer, Non-small-cell lung cancer and the tag biomarker.
Shares therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF), Next-generation sequencing (NGS), Colorectal cancer, Non-small-cell lung cancer and the tag biomarker.
Shares FoundationOne CDx / Liquid CDx, Next-generation sequencing (NGS), Endometrial cancer, Triple-negative breast cancer (TNBC) and the tag biomarker.