Testing for somatic variants of AKT1 and PTEN in breast cancer

Background to AKT1 and PTEN testing in breast cancer

This is to let you know of an addition to the molecular testing service for selected patients with advanced breast cancers in the NEY GLH which will go live from 23rd June 2025.  In the June 2025 version 13 of the national cancer test directory (see https://www.england.nhs.uk/publication/national-genomic-test-directories) somatic testing for variants in the AKT1 and PTEN genes was added for those patients with breast cancer where molecular testing will aid in patient diagnosis or management, as in the table below:

Around 40%-50% of patients with advanced breast cancer who are hormone receptor postive/HER2 negative have PIK3CA and AKT1 pathway variants. The recent availability via AstraZeneca of the drug Truqap (Capiversatib) to target those with PIK3CA/AKT1/PTEN variants, coupled with approval on the national cancer test directory, means that requesting for this test can now commence.

We will test for small variants and fusions in all the essential and clinical trials targets in table 1 in a single assay.

Please note that this assay is currently ONLY validated for detecting PTEN small variants and NOT PTEN copy number variants (approximately 40% of all PTEN loss of function variants). Validation of this assay is ongoing and expected to be completed by mid-July 2025. As such, any samples received between 23rd June and 14th July which do not have a PIK3CA or AKT1 variant will have PTEN CNV analysis activated and reported separately.

Sample requirements

What to send

• We request samples with >20% estimated tumour cell percentage: please send one tube (Eppendorf or Universal) containing 5-10 x 10μm FFPE curls.
• For samples with lower overall tumour percentage: if there is a region of the block with >20% tumour, please either; a. macrodissect tumour-rich regions and send in a single tube (preferred), or b. send 10 x 5μm slide mounted sections along with marked H&E with tumour rich area(s) marked.
• If it is not possible to macrodissect out a tumour rich region >20%, please contact the laboratory for further guidance as to whether the sample can still be tested.

Where to send to

Samples should be sent to your local genomics laboratory (see table 2 below) using the GLH solid cancer referral form (Referral Forms – North East and Yorkshire Genomic Medicine Service North East and Yorkshire Genomic Medicine Service). Please ensure that it:

• Includes email addresses for your Cell Path secretaries and pathologist. Results will be returned to the pathologist for integration into the full histopathology report and should not be acted upon out of context of those findings;
• Clearly specifies which tests are needed, including M code(s);
• Clearly specifies tumour cell nuclei as a percent of nucleated cells.

Testing and reporting

Sequencing of samples will continue to be undertaken by the GLH in Leeds using the ThermoFisher Scientific Oncomine™ Precision Assay gene panel. Results will be reported by your local genomics laboratory in PDF format to the referring centre histopathology contacts provided. We will aim to issue reports within 14 days of sample receipt.

For any questions about the above changes, please contact the Sheffield cancer genomics team at [email protected].

Limitations of testing

Please note that this testing will not detect PIK3CA, AKT1, ERBB2 or MET copy number changes.

Table 2. NEY GLH genomics labs contact details

Yours sincerely

Paul Roberts – Solid Cancer Scientific Lead NEY GLH [email protected]
Gavin Cuthbert – Cancer Lead, Newcastle Genetics Laboratory [email protected]
Rebecca Pollitt – Cancer Lead, Sheffield Genetics Laboratory [email protected]
Julie Atkey – Cancer Lead, Leeds Central Genetics laboratory [email protected]
Alistair Greystoke – Clinical lead for Cancer – NEY GLH, [email protected]