Focusing on Personalised Medicine

BRCA TESTING

Approximately 7-10% of breast and ovarian cancers are hereditary. BRCA1 & BRCA2 tumor suppressor account for a high number of these cases, but it is known that other hereditary cancer related genes are associated with the risk of developing breast and/or ovarian cancer. The BRCA Plus panel assesses 12 genes known to harbour mutations related to breast and/or ovarian cancer. The BRCA Plus analysis may identify the underlying genetic mutations that are unique to your cancer. This can help provide information on potential therapeutics, resistance to therapeutics, clinical trials and new treatments you may be able to access.

What is BRCA1 & BRCA2 Testing?

Around 5 – 10 % of breast cancers result from a mutation in the BRCA1 and BRCA2 genes. BRCA mutations increase the risk of developing breast and ovarian cancer, and patients with BRCA mutations tend to develop breast cancers at a younger age. Mutations in the BRCA genes can be sporadic, but they are often germline, meaning they are in all cells in your body and may be passed down to your children. Testing can be performed on a buccal swab sample which may indicate if there is a germline mutation in the BRCA gene. If the mutation is germline, family members can be tested to see if they have inherited the mutation, allowing earlier detection and prevention.

BRCA Plus testing can be performed off somatic samples (tissue) in patient currently diagnosed with cancer or germline samples (blood) samples in patients who are at an elevated risk of developing cancer.

Why is it important to have genomic testing if I have a family history of cancer?

Testing for Inherited cancer syndromes informs clinical decision making and may assist in the prevention of adverse health out- comes. BRCA1 and BRCA2 are part of complexes involved in DNA repair using homologous recombination. Women with an abnormal BRCA1 or BRCA2 gene have up to an 80% risk of developing breast cancer by age 90 and up to 55% risk of developing ovarian cancer. In addition to breast cancer, mutations in the BRCA1/2 gene also increase the risk of ovarian, fallopian tube, pancreatic cancer, gastric cancer and prostate cancers.

If there is a family history of breast cancer, other members of your family can undergo genomics testing to see if they are a carrier of germline BRCA mutations. If they are identified as a carrier of the mutations, this can enable them o:t • Start cancer screening tests earlier • Get screened for that type of cancer more often • Get screening tests that are used only for people known to be at increased cancer risk • Watch yourself closely for signs or symptoms of that kind of cancer • Learn about options to help reduce the risk of certain types of cancer, such as drugs or surgery

How do I organise Testing?

Download Request Receive testing kit Genomics For Life Genomics For Results sent to Form and complete from Genomics receives sample Life completes nominated health and return to for Life for testing requested testing care professional *Or Genomics For Life will arrange Genomics For Life retrieval of a tissue sample from your most recent biopsy.

Toll Free: 1800 445 433 Fax: 1300 658 893 Email: [email protected] Web: www.genomicsforlife.com.au Dear Doctor,

Y our patient is exploring genetic testing for their cancer and has requested Genomics For Life to perform tumour profiling .

Genomics For Life is a fully NATA accredited, TGA approved, clinical diagnostic laboratory located in Brisbane. It offers a complete range of genomic testing services including comprehensive molecular tumour profiling. The service is performed with the support of the patient’s referring Doctor.

Si nce 2013 we have been offering and developing a sequencing service provision for both Australian and International patients. During this time we have observed how patient outcomes can be improved when information, support and analysis are provided to both the patient and the patient’s medical team throughout the entire process of genomic testing.

There are many advantages for genetic testing a patient’s tumour sample including but not limited to the following:

1. Cancer gene profiling is a powerful diagnostic tool, which may provide complimentary drug target information to the standard therapies that may have been considered or completed to the patient to date. 2. Our Genomic service comprehensively analyses the DNA and RNA of the tumour and may identify mutations that are unique and may provide prognostic and predictive information. 3. The clinical interpretation, provided by Genomics for Life, takes into account both local and up-to-date international protocols for treatment options. 4. Genomic testing provides a personalised approach to cancer treatment, which may improve patient outcome. Clinical trials of over 70,000 patients have shown that personalised therapy, based on genomic profiling of tumours, is the most effective way to improve outcome, with higher response rates, longer progression free and overall survival, and fewer deaths related to adverse events across cancers. [1-3] 5. Investing in Genomic testing may save time and money that may be spent on non-targeted/unproductive therapies.

There are also a few important things to note:

1. In the majority of cases, the cost of genomics testing, is not covered by Medicare, but in some cases private health insurance may pay some benefits. We encourage the patient to check with their private fund provider. 2. Our comprehensive reports will show potential treatment options, regardless of the PBS listing, which may mean the patient may be out-of-pocket for treatment if they decide to proceed with these treatment options. 3. In some cases, the results may have implications for other family members if a clinically significant germline variant is identified. 4. Our laboratory fulfils all the local regulatory requirements to be able to offer these tests, and there is local support and interpretation of its results

Genetic counselling can be arranged for your patient, by health care professionals that are conversant in genetic testing. Information can also be provided about access to clinical trials both in Australia and overseas, if required.

Additional information is available on our website: www.genomicsforlife.com.au, including details on our comprehensive testing menu, including response to immune checkpoint inhibitors and cell-free (liquid biopsy) based assays. The FAQ’s contain more information on how Genomics testing may assist patient care and details of the processes involved in testing.

Prior to proceeding with testing, we encourage the patient to discuss with us their budget and testing options, to ensure that we offer a solution that is both economically viable for the patient and useful for the medical practitioner.

If you would like to contact us, to further discuss testing, please don’t hesitate to call us on 1800 445 433 or via email at [email protected]

Kind regards, Genomics For Life 1. Jardim, D. L., et al. (2015). “Impact of a Biomarker-Based Strategy on Oncology Drug Development: A Meta-analysis of Clinical Trials Leading to FDA Approval.” J Natl Cancer Inst 107(11). 2.ReferencesSchwaederle, M., et al. (2015). “Impact of Precision Medicine in Diverse Cancers: A Meta-Analysis of Phase II Clinical Trials.” J Clin Oncol 33(32): 3817-3825 3. Subbiah, V. and R. Kurzrock (2016). “Universal genomic testing needed to win the war against cancer: Genomics is the diagnosis.” JAMA Oncology 2(6): 719-720

Phone: 1800 445 433 | Fax: 07 3054 4363 | Email: [email protected] | Web: www.genomicsforlife.com.au SOMATIC MUTATION TESTING

REQUEST FORM Accredited for compliance with NPAAC Standards and ISO 15189 NATA Accreditation Number: 19325

PATIENT DETAILS ORDERING MEDICAL PRACTITIONER DETAILS

Patient Surname: Doctor Name:

Patient Given Name(s): Provider Number:

DOB: ____ / ____ / ______Male Female Practice Name:

Patient Address: Practice Address:

Contact Number: Contact Number:

Email: Fax:

Medicare Details: Email (for results):

PATIENT INFORMED CONSENT STATEMENT MEDICAL PRACTITIONER CONSENT STATEMENT

I agree to the genetic analysis and the release of my tissue and/or other By signing this form, I confirm to the best of my knowledge that I have the samples for testing. consent of the patient to request somatic and/or germline testing, and that the patient is aware that this test may require pre-payment prior to commencement of the test.

Patient’s Signature: Doctor’s Signature:

Date: Date:

PRIVACY NOTE: The information provided will be used to assess any Medicare Beneft payable for the services rendered and to facilitate the proper administration of government health programs, and may be used to update enrolment records. Its collection is authorised by provisions of the Health Insurance Act 1973. The information may be disclosed to the Department of Health and Ageing or to a person in the medical practice associated with this claim, or as authorised/required by law.

CLINICAL INFORMATION

Please attach all relevant patient history and pathology reports Metastatic Disease: Yes No

TEST(S) REQUESTED

Comprehensive Plus Solid Tumour Analysis TSP 23TM : Melanoma, Lung & Bowel Cancer Targeted Assay

Transcriptome Analysis Inherited Cancer Assay

Tumour Mutational Burden Assay Cell-Free DNA Testing (dPCR - Single Probe)

Sarcoma Assay Cell-Free DNA Assay PanCancer Assay Lung Assay Homologous Recombination Deficiency (HRD) Assay Colon Assay Breast Assay

BRCA Somatic Assay Pharmacogenomics

BRCA Germline Assay Other:

Please complete all the above fields. Once the Test Requesition Form has been completed, please return to Genomics For Life along with the sample. Patient must sign consent form to perform the test.

Billing Information Collection Staff Only Laboratory Use Only

NOTE 1: Payment must be cleared prior to testing being performed, unless Medicare rebateble. Collection Sample Rec. Sample Type: NOTE 2: There may be out-of-pocket expenses for retrieval of slides imposed by other laboratories that may Date: Type: Date: (Exp Date) be charged to the patient. NOTE 3: Laboratory will contact you prior to the commencement of testing to arrange payment. Credit card Collection Collector’s Rec. Rec. payments will incur a surcharge. Direct Debit option is available. Time: Signature Time: By:

GFLADM-1222307366-204 Phone: 1800 445 433 Fax: 07 3054 4363 Email: [email protected] Mail: PO Box 1201 Milton QLD 4064 Version: 4.0 Review Date: 24/05/2023 SOMATIC MUTATION TESTING REQUEST FORM Accredited for compliance with NPAAC Standards and ISO 15189 NATA Accreditation Number: 19325

TESTING OPTIONS SAMPLE TYPE

Comprehensive Plus Solid Tumour Analysis - Targeted sequencing (NGS) assay that enables the detection of relevant SNVs, CNVs, gene fusions, and indels from 500 unique genes. Also includes Tumour Mutational Burden, Homologous Recombination Tissue Deficiency and Microsatellite Instability.

Transcriptome Analysis - This assay assesses the mRNA expression of 20809 genes which can provide complementary information to DNA testing. Integrative sequence analysis provides a clinically relevant, multi-dimensional view of the complex molecular landscape and microenvironment of cancers. Gene expression profiles help assess the functional status of critical pathways. Specific mutations in cancer-associated pathway genes, like those of the NOTCH, WNT–beta-catenin, SHH (sonic hedgehog Tissue gene), and HIPPO pathways, can be assessed for functional consequences in terms of expression levels of their downstream target genes. This type of testing has been shown to potentially increase the number of targetable pathways and provide prognostic information and improve classifications of tumours.

Tumour Mutational Burden - Our report collates available information, previously identified through histology and PD-L1 staining, Tissue combined with genetic analysis of 409 cancer driver genes, to provide a likelihood of response to Immune Checkpoint Inhibitors.

Sarcoma Assay - The Sarcoma Assay is a targeted sequencing assay that simultaneously detects and identifies gene fusions associated with soft tissue cancers. This panel is particularly useful in correctly diagnosing potential sarcoma tumours which then can Tissue correctly identify possible drug targets for treatment.

Homologous Recombination Deficiency (HRD) Assay - Includes analysis of genes associated with HRD and HRR pathways, Tissue including BRCA1, BRCA2, ATM, CHD1, CHEK2, NBN, PALB2, RAD51C, RAD51D, RAD51L3-RFFL, SMARCA4 and TP53 genes.

TSP 23TM: Melanoma, Lung & Bowel Cancer Targeted Assay - Targeted Sequencing Panel covering 23 genes involved in lung Tissue cancer, bowel cancer and melanoma. Does not include CNVs or Tumour Mutational Burden. (Medicare Rebate may apply)

Kids Cancer Targeted Therapy Assay - Includes a large 97-gene translocation/fusion panel, as gene fusions and copy number alterations are more common in childhood cancers. Also includes an 82-DNA target panel with comprehensive coverage of all relevant mutations, 44 targets with full exon coverage, specifically tumour suppressor genes, and 24 CNV targets, including several key driver Tissue DNA mutations that have been described in different paediatric tumours. This panel can also be used for adult tumours depending on the tumour type.

BRCA Plus Assay - Includes analysis of BRCA1 & BRCA2, as well as 9 other genes commonly associated with Breast and Ovarian Cancers - ATM, CHD1, CHEK2, NBN, PALB2, RAD51C, RAD51D, RAD51L3-RFFL, SMARCA4, TP53 Tissue or Blood • Germline (Blood) - Includes NGS and MLPA on BRCA1 and BRCA2 (Medicare Rebates may apply) • Somatic (Tissue) - NGS Only (No Medicare Rebate available)

Inherited Cancer Panel - Various Multi-gene panels specific for Pancreatic, Breast, Ovarian, Endometrial and Colorectal Cancers Blood including CNV (Medicare rebates may apply)

Pharmacogenomics - Comprehensive Analysis of 40 drug metabolism enzymes designed to give information on metabolism of all Blood drug classes including oncology drugs. This can indicate the likelihood of an adverse drug reaction.

TCR-Beta Assay - T-cells can recognise foreign particles through their T-cell receptors (TCRs), which have variable ends enabling the recognition of millions of foreign molecules. This test looks at all the different T-cell receptors in the patient’s sample (TCR repertoire), assessing diversity and clonal expansion. This can determine how your immune system is recognising and responding to the cancer. Tissue or Blood The assay can be used to assess if the immune system is recognising the tumour and generating more cells directed at fighting the tumour. This test can be used on a blood sample or a tumour tissue sample and follow up testing can help determine if immune checkpoint inhibitors are working. This is a measure of what is occurring in the patient rather than a prediction of what may occur.

Cell-Free assays are useful for early detection of relapse & response to therapy. Cell-Free assays an also be used when tissue biopsy is not an option. This testing can identify mutations at levels below 1%

cfDNA™ (dPCR) - Mutation Tracking analysis using blood samples – eg EGFR T790M. Other single point known mutations are Blood available - please contact us for further information.

Cell-Free DNA PanCancer Assay - The analysis of 52 genes and 96 fusions. Includes CNVs for 12 genes, such as EGFR and MET. Changes in cell-free DNA occur in response to therapy including immune checkpoint inhibitors and this test can aid in evaluating Blood response.

Cell-Free DNA Lung Assay - 12 genes found in lung cancer including genes associated with resistance including RET, ALK and Blood ROS-1 fusions and CNVs, MET including exon 14 skipping

Cell-Free DNA Breast Assay - 12 genes including CNVs for CCND1, ERBB2 and FGFR1 Blood

Cell-Free DNA Colon Assay - 14 genes including AKT1, APC, BRAF, CTNNB1, EGFR, ERBB2, FBXW7, GNAS, KRAS, MAP2K1, NRAS, Blood PIK3CA, SMAD4, TP53

For further information on our available tests, please contact Genomics For Life or visit our website. If you are unsure which test(s) are best suited for your patient, please contact Genomics For Life and we can help determine which test(s) would be beneficial for their particular clinical circumstances. GFLADM-1222307366-204 Phone: 1800 445 433 Fax: 07 3054 4363 Email: [email protected] Mail: PO Box 1201 Milton QLD 4064 Version: 4.0 Review Date: 24/05/2023