Breast cancer focused gene panel

Also known as: Breast panel, AKT1, ERBB2 (HER2), ESR1, PIK3CA

Test category:

Oncology – Breast adenocarcinoma

Use of test

Purpose:
The breast cancer focused gene panel includes genes relevant to therapy in breast adenocarcinoma: ERBB2 point mutations/indels; mutations in genes in the PI3K/AKT/mTOR pathway (AKT1 and PIK3CA) and resistance mutations in the oestrogen receptor (ESR1) gene.
Note that the breast cancer focused panel does not currently include BRCA1/2, or other homologous recombination repair genes.
Utility:

ERBB2 (HER2) activation in breast cancer is typically caused by gene amplification, which can be detected by in-situ hybridisation. However, in approximately 3-5% of cases, there is no gene amplification and the activating mutation is a point mutation or insertion/deletion mutation (indel). The utility of anti-HER2 agents is not yet well established in this setting, but presence of an atypical ERBB2 activating mutation may allow access to clinical trials.

Activation of the PI3K/AKT/mTOR pathway is known to occur in both hormone receptor positive (HR+) and HER2+ breast cancer. In patients with HR+ tumours that have developed resistance to endocrine therapy, alpelisib plus fulvestrant is a treatment option that has been recently approved by the TGA. Presence of a PIK3CA activating mutation is a biomarker for response to alpelisib.

Finally, ESR1 ligand-binding domain mutations can arise as a resistance mechanism to treatment with endocrine therapy in HR+ breast cancer. As well as explaining acquired resistance to aromatase inhibitors, the presence of an ESR1 mutation has prognostic implications in metastatic breast cancer, and therapies that modulate mutant receptors may be available in clinical trials.

This test can be expanded to a full Find It panel that simultaneously evaluates the mutation status of tumour DNA at more than 140 well-characterised positions (hotspots) and more than 20 exons in no less than 30 cancer-associated genes.

Ethical considerations:

This assay is designed to detect non-heritable mutations. It does typically not raise issues of ethics or consent that are different from most other investigations ordered in the routine care of a patient.

Methodology:

Targeted analysis of clinically relevant mutations in AKT1 (codon 17), ERBB2 (G309, S310, L755, exon 20), ESR1 (K303, S463, codons 534-538) and PIK3CA (R88, codons 542-549, codons 1043-1049).  This assay detects targeted single nucleotide variants and insertion/deletion mutations (of up to 24 base pairs in size). Fusion genes and copy number variants will not be detected. BRCA1/2 and other homologous recombination repair genes are not tested. Very low level targeted variants (<5% variant allele frequency) may not be detected.

For further details, please refer to the description of the full Find It panel.

Requesting the test

Ordering:

This test is usually requested by a surgeon or oncologist. Please use the specific request form (see link below).

Request Form:

Download the somatic mutation request form.

Sample required:

Formalin-fixed, paraffin embedded tissue (FFPE) - 15 sections of 4 uM thickness, dried overnight at 37°C onto charged/coated slides.

Special instructions:

Please label each slide with patient and block identifiers plus number them sequentially 1-15. Stain slides 1 and 15 with H&E and leave slides 2 to 14 unstained. The request should be accompanied by the somatic mutation request form (above) and a copy of the original histopathology report.

Turnaround time:

7 business days from receipt of sections by the testing laboratory.

Price:

$350.

Rebate:

No MBS rebate is available for the Breast cancer focussed panel.

 

Click here for our billing policy.