Everything Genetic 12 Gene Breast Cancer Panel

• ATM
• BARD1
• BRCA1
• BRCA2
• CDH1
• CHEK2
• PALB2
• PTEN
• RAD51C
• RAD51D
• STK11
• TP53

A personalised results report will be sent to the customer and made available to their clinician (upon the customer’s consent).

There are three possible result outcomes from this test:

1. A variant detected result – a pathogenic or likely pathogenic variant has been detected

1. A Variant of Uncertain Significance (VUS) result

1. A negative result – no pathogenic variant detected

Variant detected: In cases where a patient has already been diagnosed with breast cancer, a variant detected result will mean that a pathogenic or likely pathogenic variant (a fault in a gene) has been found. Therefore, they have an increased risk of developing breast or ovarian cancer as a second primary.

If taking the test to understand an individual’s risk of developing breast cancer, a variant detected result will also mean that a fault in one or more of their genes has been found. Therefore, they have an increased risk of developing breast or ovarian cancer.

View a copy of a sample report here >>

Negative: If the patient has already been diagnosed with breast cancer; a negative result will mean that the test has not identified a pathogenic variant in the genes analysed (no fault in the genes). Therefore, they have no variants in the genes analysed that put them at high risk of developing breast or ovarian cancer as a second primary.

However, if an individual is taking this test to understand their risk of developing breast cancer, a negative test result will mean that the test has not identified any faults in the known genes. Therefore, they have no variants in the genes analysed that put them at risk of developing breast or ovarian cancer.

View a copy of a sample report here >>

Variant of Uncertaine Significance: The test result could show you have a Variant of Uncertain Significance (VUS). This means that the test has identified a change in the sequence of one of your genes, but it is not yet known if that indicates a clinically significant breast cancer risk. However, it is unusual to receive a VUS result on any of these genes.

View a copy of a sample report here >>

No personal medical guidance is provided with the test result. This should be obtained directly from the clinician.

Who can order this test from Everything Genetic? Healthcare providers and patient referrals/individuals.

Turnaround time: 2 – 3 weeks from receipt of sample in laboratory [1]

Preferred specimen: Non-invasive simple saliva sample using Oragene OG-610. 

Alternative specimen collection: Blood. Please use your own EDTA purple top tube (we accept both K2EDTA and K3EDTA). Minimum volume requirement is 3mL for a 10mL tube and 2mL for a 4mL or 6mL tube. 

Delivery information: Test kits will be sent out by using a Royal Mail Tracked service, unless otherwise arranged. 

[1] MLPA performed on all suspected CNVs may require a longer turnaround time.

Pre and post-test clinical support is mandatory for those taking the test. This can either be provided by the clinician treating the patient/individual or Everything Genetic’s medical team.

Pre and post-test clinical support provided by Everything Genetic is included in the testing service price. However, if it is provided by a private clinician, the patient/individual taking the test may be charged an additional fee for this service which is at the clinician’s discretion.

This unique and personal clinical support service offered by Everything Genetic provides patients and their relatives the guidance and support they need so they understand their results and what they should do next.

Everything Genetic’s pre-test clinical support is provided through a clinically guided informational video which explains:

• What the test is for
• Why patients should take the test
• What it does and doesn’t test for
• What the possible results are from taking the test

If the results show a negative or VUS result, the patient will receive a clinically guided information video explaining what the results mean and what they should do next. A results report will also be sent to the patient and/or clinician via email, with the option of speaking to our medical team.

If the results show a variant detected result, a private consultation will be arranged with either our medical team or the clinician who referred them. Following the consultation, a results report will be sent via email.

For clinicians who provide their own pre and post-test clinical support, the results will be sent directly to them.

Read more about our pre and post-test clinical support service >>  

A woman born after 1960 and living in the UK has an estimated 1 in 7 lifetime risk of developing breast cancer. Approx. 15-20% of women with breast cancer will have a family history of the disease.

Inherited variants in BRCA1 and BRCA2 genes account for about  4-6% of all breast cancer cases in women. 5–10% of breast cancers are thought to be hereditary caused by abnormal genes passed from parent to child. BRCA1 and BRCA2 are the most common. The lifetime risk of developing ovarian cancer is estimated at 28-44% for women with the BRCA1 gene mutation, and 27% for women with the BRCA2 gene mutation.

The other genes in this panel are also associated with a significant risk of breast and ovarian cancer, and their inclusion is expected to increase the clinical sensitivity of this test. Individuals with a pathogenic variant in one of these genes have a significantly increased risk of developing breast and ovarian cancer.

The identification of these individuals opens the door for tailored screening, early detection and prevention of cancer.

Breast cancer patients who have these genes can benefit from customised surgical treatments and targeted drug therapies, which can lead to an improvement in survival outcomes.^[2]

Limitations

The genetic results are interpreted in the context of the provided clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the provided genetic data or patient information is inaccurate and/or incomplete. If the obtained genetic results are not compatible with the clinical findings, additional testing should be considered.

More complex genetic events such as inversions, translocations, and repeat expansions, are not analysed in this test. In addition, due to technology limitations, certain regions may be poorly covered, or not covered at all. In these regions and others encompassing repetitive, high homology (such as pseudogene homology), and GC-rich sequences, relevant variants can be missed.

The Copy Number Variation (CNV) detection software has a sensitivity of more than 95% for all homozygous/ hemizygous deletions, as well as heterozygous deletions/duplications and homozygous/hemizygous duplications spanning at least three consecutive exons. Sensitivity of more than 90% for CNV calling is expected including for single exon. The CNV detection sensitivity is decreased for repetitive and homologous regions, such as pseudogenes. Heterozygous CNVs spanning less than three exons cannot reliably be detected. In cases with low quality DNA, CNV analysis may not be possible to perform.

Potential aberrant splicing is assessed with splice prediction tools. Intronic variants that are beyond 10 nucleotides from exon-intron boundaries are not considered for aberrant splicing analysis, with the exception of known pathogenic splicing variants evidenced by external sources.

References:

• NICE Ovarian cancer: what are the risk factors? – see here >>
• Breast Cancer UK
• Cancer Research UK