Guide for health professionals ordering genetic testing

eviQ protocols do not apply to community screening for genetic disorders (e.g. testing people who have not had a cancer/tumour and do not have a significant family history of cancer).

Predictive tests (i.e. testing for a pathogenic variant already identified in the patient’s family) should be coordinated by a clinical genetics service or familial cancer centre. There is a much higher chance of detecting a pathogenic variant when the familial variant has already been identified, and therefore a higher potential for complex outcomes, with profound clinical psychosocial and ethical implications for some individuals and their families.

Predictive genetic tests in people who have not had cancer require specialised knowledge, specific written consent, and professional genetic counselling to precede and accompany the test.^r The Human Genetics Society of Australasia (HGSA) has a Position Statement on Predictive and Pre-symptomatic Genetic Testing in Adults and Children.

Genetic testing may be warranted in an unaffected individual where there is a strong suspicion of a hereditary cause due to family history, but genetic testing has not been possible due to appropriate relative being deceased. This requires careful assessment by the clinical genetics/familial cancer clinic including verification of pathology records for affected relatives.

It is the consensus of the eviQ cancer genetics reference committee that genetic testing is recommended when the probability of identifying a clinically actionable germline class 4 or 5 variant in a cancer and/or tumour predisposition gene^* is 10% or more. The eviQ cancer genetics reference committee (RC) has developed a consensus list of clinically actionable genes associated with familial cancer risk where pathogenic variants are clinically actionable for diagnostic and/or predictive gene testing.

* In some cases, a combined probability of identifying a clinically actionable pathogenic variant in two or more genes using panel testing will be considered.

There must be sufficient available published peer-reviewed evidence to:

• confirm a clinically relevant causal association between the gene being tested and the cancer(s) under consideration
• establish the probability of identifying a class 4/5 variant
• quantify associated health risks
• inform management recommendations for the patient and/or family.

“Clinically actionable” includes one or more of the following:

• broad management implications for the patient
• where presymptomatic testing of relatives would change management (surveillance and/or risk-reducing surgery)
• family planning implications.

Individuals fulfilling the above criteria for genetic testing may be offered a panel which includes additional genes with a <10% probability when the findings in those genes would also be clinically actionable. When choosing a cancer gene panel, care should be taken to select genes that have both clinical validity and clinical utility for the phenotype of concern. The likelihood of identifying a variant of uncertain significance increases as the number of genes included in a panel increases. eviQ provides information about genetic testing using cancer gene panels for adults and paediatrics.

Genetic testing to inform the management of a person with a cancer or tumour may also be referred to as "treatment-focused genetic testing", "mainstream genetic testing" or "oncogenetic testing". The development of genetic testing protocols that are primarily to inform therapy (i.e. treatment-focused genetic testing) is outside the remit of the eviQ cancer genetics RC and should be managed by eviQ RCs with cancer treatment expertise (e.g medical oncology RC, haematology RC). Support from the eviQ cancer genetics RCs can be sought for the development of treatment-focused genetic testing protocols. eviQ cancer genetics protocols are guides only.

State- and territory-based genetic testing information

Non-genetic health professionals planning to order genetic testing should liaise regularly with their local or state/territory clinical genetics service or familial cancer centre for specific advice and information. 

Ordering the appropriate test 

It is ideal that a co-ordinated approach is undertaken to maximise the clinical utility of genetic testing from both a treatment focussed and familial cancer perspective (e.g. if only two genes are relevant from a treatment perspective but a larger gene panel is relevant from a familial cancer perspective, it is preferable that the larger gene panel be ordered upfront).

The ordering clinician is responsible for ensuring that the test they order is the appropriate test for the patient. Copy number variants (CNV’s, where all or part of a gene is deleted or duplicated) contribute to a clinically significant proportion of the pathogenic variants associated with familial risk of cancer. Not all available cancer panels offer CNV analysis. Furthermore, there are certain genes for which comprehensive testing requires specialised technology beyond what is offered by a standard cancer gene panel (e.g. long range PCR for the mismatch repair gene PMS2). Advice should be sought from the local clinical genetics service or familial cancer centre if there is uncertainty regarding this issue.

Education

Online e-learning for health professionals is available from the Clinical Oncology Society of Australia (COSA) Familial Cancer Special Interest Group. These modules provide education about ordering BRCA1 and BRCA2 gene testing in patients with breast or ovarian cancer, but the principles can be applied to testing for other cancer predisposition genes.

Consent

It is recommended that all patients who undergo genetic testing provide their informed consent, ideally in writing, in a manner that meets state/territory/hospital medicolegal requirements. Patients should be informed that:

• the results of genetic testing may assist in deciding their current or future health management
• the results of genetic testing can have implications for their biological relatives
• there may be costs associated with genetic tests that are not covered by Medicare (and how much the patient will be expected to pay)
• genetic testing is voluntary and that they can decline or defer testing, and
• potential outcomes of testing might include:
  • no reportable variants
  • a variant of uncertain significance (class 3 variant, sometimes called an "unclassified variant")
  • a pathogenic variant or likely pathogenic (class 5 or class 4) variant identified
  • an incidental finding of a variant in a gene (or genes) unrelated to the reason for testing.

An example National Clinical Consent form for genomic testing has been developed by Australian Genomics. NSW Health clinicians should continue to use consent forms specific to that state.

Patients should be referred to their local clinical genetics service or familial cancer centre regardless of the outcome of treatment-focused testing where:

• they require additional specialised genetic counselling prior to or after testing
• a pathogenic variant or likely pathogenic variant is identified
• a variant of uncertain significance is identified, especially in the context of a strong family history of cancer (where family segregation testing may help to reclassify the variant), or
• they have a significant personal or family history of cancer that has not been explained by the result.

Additional information relevant to tumour genetic testing

The following resources have been developed to assist clinicians ordering tumour genetic testing to guide treatment decisions for their patient:

ID 4251 Germline testing in individuals for whom BRCA1 and BRCA2 tumour testing may inform systemic therapy options

ID 4056 Considerations for germline testing for variants identified in solid tumours

• National Clinical Consent form for genomic testing developed by Australian Genomics is available for adaptation and use by clinical genetics services and health professionals responsible for guiding patients through the consent process for whole exome, whole genome or panel testing. Note: NSW Health clinicians should continue to use consent forms specific to that state
• Online e-learning for health professionals is available from the Clinical Oncology Society of Australia (COSA) Familial Cancer Special Interest Group. These modules provide education about ordering BRCA1 and BRCA2 gene testing in patients with breast or ovarian cancer, but the principles can be applied to testing for other cancer predisposition genes
• Information for patients from the Centre for Genetics Education

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Version 3

Date

Summary of changes

13/11/2023

Guide reviewed out of session via Teams with the following changes made: Genetic testing in people who have not had a cancer/tumour: Addition of "Genetic testing may be warranted in an unaffected individual where there is a strong suspicion of a hereditary cause due to family history, but genetic testing has not been possible due to appropriate relative being deceased. This requires careful assessment by the clinical genetics/familial cancer clinic including verification of pathology records for affected relatives." Genetic testing in cancer/tumour affected individuals: addition of "a familial cancer perspective" to accordion title Genetic testing to inform cancer/tumour treatment: Addition of "ordering the appropriate test" and "additional information relevant to tumour genetic testing". Version updated to V.3. Review in 2 years.

Version 2

Date

Summary of changes

31/03/2021

Guide reviewed by the cancer genetics reference committee chairs for the March 2021 reference committee meeting with the following changes made: Note changed from "Probability may be combined using several genes, e.g. for BRCA1 and BRCA2 a combined probability is used." to "In some cases, a combined probability of identifying a clinically actionable variant in two or more genes using panel testing will be considered." Genetic testing in cancer/tumour affected individuals: Bullet 1: "clinical relevant" changed to "clinically relevant" Genetic testing to inform cancer/tumour treatment: Under State- and territory-based genetic testing information: "should contact" changed to "should liaise regularly with" Under Consent: Bullet 5: "potential outcomes of testing include" changed to "potential outcomes of testing might include" Version updated to V.2. Review in one year.

Version 1

Date	Summary of changes
12/08/2020	New resource developed and discussed at the cancer genetics paediatric reference committee July 2019 and the cancer genetics reference committee October 2019 meetings. Discussions continued via email. Protocol approved for publication as V.1. Review in 1 year.