biomarkersBiomarker

PIK3CA mutation

aka PIK3CA mutation, PIK3CA-mutated, PIK3CA H1047R, PIK3CA E545K, PIK3CA E542K, PIK3CA hotspot, PI3K mutation breast cancer

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.

Part ofPIK3CA / PI3K-alpha· PIK3CA All readouts

PIK3CA / PI3K-alpha: what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

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.

Sequencing 3 approval thresholds

What it means for a patient

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.

Scoring rule

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

Thresholds used in approvals

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

Drugs whose label names it

Alpelisib Inavolisib Capivasertib

Companion diagnostics (FDA list)

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	Capivasertib Fulvestrant	P170019/S048 (11/16/2023)

Tests that measure it

FoundationOne CDx FoundationOne Liquid CDx therascreen PIK3CA RGQ PCR Kit Tempus xT and xT CDx FoundationOne CDx FoundationOne Liquid CDx Caris MI Cancer Seek Guardant360 CDx

Trials that name this readout

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.