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HRR Mutations, Including BRCA1/2 in Prostate Cancer

Optimize HRRm testing in prostate cancer with guideline recommendations and actionable best practices.

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Clinical Relevance of HRR Mutations, Including BRCA1/2

In the presence of homologous recombination repair (HRR) gene mutations, tumor cells are unable to effectively repair double-strand breaks (DSBs) in DNA, leading to the persistence of DSBs, accumulation of mutations, and ultimately, carcinogenesis.1,2 In prostate cancer, one way to assess HRRm status is through individual mutations in BRCA1 or BRCA2.3

Patients with metastatic prostate cancer and certain HRR mutations risk poorer
outcomes4,5

Graph showing the median survival time for patients with BRCA1, BRCA2 or ATM mutations as three years whereas for patients without BRCA1, BRCA2 or ATM mutations the median survival time is six years.

Median survival time for patients with and without BRCA1, BRCA2, or ATM mutations4

BRCA1, BRCA2, or ATM mutations (n=10)

3
years

No mutations (n=112)

6
years

ATM, ataxia-telangiectasia mutated; BRCA1/2, BReast CAncer susceptibility gene 1/2; DNA, deoxyribonucleic acid; DSB, double-strand break; HRR, homologous recombination repair.

Checklist icon

HRR Mutation Testing Recommendations

NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) for Prostate Cancer recommend tumor testing for all patients with metastatic prostate cancer3

Why test3Whom to test3What to test3How to test6

To aid in treatment decisions, clinical trial enrollment, and/or familial risk counseling

All patients with metastatic prostate cancer at metastatic or initial diagnosis

Somatic HRR gene mutationsa including BRCA1/2

FDA-approved assay:

  • FoundationOne®CDx
    (Foundation Medicine, Inc.)

Germline mutations in BRCA1/2

FDA-approved assay:

  • BRACAnalysis CDx®
    (Myriad Genetic Laboratories, Inc.)

When metastatic biopsy is unsafe or unfeasible, ctDNA assay is an option

    FDA-approved assay:

    • FoundationOne® Liquid CDx (Foundation Medicine, Inc.)

    This document is intended as educational information and is not intended as a complete list of available testing options. AstraZeneca is not responsible for any test provider and does not endorse any particular diagnostic test. The accuracy and results of diagnostic tests vary, and AstraZeneca shall have no liability arising from such testing. Information provided herein should in no way be considered a guarantee of coverage, reimbursement, or patient assistance. Providers should contact third-party laboratories for information on their patient assistance programs. While diagnostic testing may assist providers in identifying appropriate treatment for patients, the decision and action should be decided by a provider in consultation with the patient. All products are trademarks of their respective holders, all rights reserved.

    Footnotes

    aHRR genes such as: BRCA1, BRCA2, ATM, PALB2, FANCA, RAD51D, CHEK2, and CDK12.3

    ATM, ataxia-telangiectasia mutated; BRCA1/2, BReast CAncer susceptibility gene 1/2; CDK12, cyclin-dependent kinase 12; CDx, companion diagnostic; CHEK2, checkpoint kinase 2; ctDNA, circulating tumor deoxyribonucleic acid; FANCA, fanconi anemia complementation group A; FDA, US Food and Drug Administration; HRRm, homologous recombination repair mutation; NCCN, National Comprehensive Cancer Network® (NCCN®); PALB2, partner and localizer of BRCA2; RAD51D, RAD51 paralog D.

    Nearly a Third of Patients Have an HRR Mutation7

    ~15% of patients have BRCA1/2 mutations7

    • A retrospective multicenter observational cohort study of patients with advanced prostate cancer in the United States from 2013 to 20197
    • 674 patients were tested for 1 or more of 6 HRR gene mutations of interest – ATM, BRCA1, BRCA2, CDK12, PALB2, and FANCA7

    As supported by real-world evidence, a substantial proportion of patients with advanced prostate cancer may have an HRR gene alteration7,8

    Bar chart showing prevalence of specific HRR gene alterations across BRCA2, CKD12, ATM, BRCA1, PALB and FANCA. The BRCA2 and BRCA1 bars are highlighted to indicate that 16% of patients have BRCA1/2 mutations

    Prevalence of specific
    HRR gene alterations (%)

    BRCA2

    13.4%

    (n=604)

    CDK12

    7.7%

    (n=273)

    ATM

    6.2%

    (n=531)

    BRCA1

    2.8%

    (n=603)

    PALB2

    1.9%

    (n=424)

    FANCA

    1.6%

    (n=251)

    In a separate study, real-world data were analyzed from routine prospective clinical genomic profiling in a US institution8


    • Using a validated assay of 395 genes (including BRCA1/2, CDK12, ATM, CHEK2, FANCA, and ATR, among others) on 3,476 unmatched primary and metastatic prostate cancer tissue samples, DNA repair pathway genomic alterations were identified in 31% of samples8

    ATM, ataxia-telangiectasia mutated; ATR, ataxia telangiectasia and Rad3-related; BRCA1/2, BReast CAncer susceptibility gene 1/2; CDK12, cyclin-dependent kinase 12; CHEK2, checkpoint kinase 2; FANCA, Fanconi anemia group A; HRR, homologous recombination repair; HRRm, homologous recombination repair mutations; PALB2, partner and localizer of BRCA2.

    Investigate DNA icon

    Sample Type Determines Somatic and/or Germline HRR Mutation Identification

    Infographic showcasing the mutations which may be identified using tumor tissue or blood samples.

    Tumor Tissue Sample

    Germline and somatica

    HRR gene panel9,10,b (includes BRCA1 and BRCA2)

    ~28% of men

    BRCA1 and BRCA211

    ~10% of men

    Among men with mCRPC who were prospectively screened for HRR gene alterations for a large prospective study (biomarker status reported for 2,792 patients)10

    Blood Sample

    Germline

    BRCA1 and BRCA212

    ~6% of men

    In a systematic review, BRCA1/2 germline mutations were determined from peripheral blood of 1,038 patients with mCRPC12

    Sample typeType of mutation identifiedSpecial considerations/limitations

    Tumor tissue13

    Germline and somatic mutations

    • Positive results should be followed by familial risk assessment (germline testing)
    • Tissue testing does not distinguish between somatic and germline mutations

    Plasma ctDNA14,15

    Germline and somatic mutations

    • Dependent on adequate levels of ctDNA
    • Does not distinguish between somatic and germline mutations

    Blood or saliva16

    Germline mutations

    • Does not identify somatic mutations
    • May have familial implications

    Tumor testing identifies both germline and somatic mutations, without differentiation7,13,16

    Tissue samples may be collected from the primary tumor site or sites of metastasis13

    • The TRUS-guided 12-core systematic biopsy method is considered gold standard for prostate tissue sample collection; however, this may yield false negatives17
    • Interventional radiologists use imaging to guide biopsy collection from a non-bone metastatic site18
    • Bone-only metastases are often sclerotic and require decalcification. Bone scans and CT imaging can identify lesions more suitable for biopsy19
    • In the event of failed tissue acquisition, archival tissue samples may be used; however, they may not reflect the current tumor molecular status13

    Consider Plasma ctDNA if Tumor Tissue Is Unavailable

    • Minimally invasive option to assess HRRm in mCRPC20
    • As the amount of ctDNA may correlate with disease progression, sample collection should coincide with progressive disease and not during therapeutic response20–22
    • High concordance between ctDNA and tissue testing for BRCA1, BRCA2, and ATM15
    Infographic demonstrating that results from ctDNA testing alone is actionable.

    A Positive
    mutation result from ctDNA testing alone is actionable15,21

    A Negative
    result requires confirmation with tissue-based testing15,21

    Checklist icon

    Perform germline testing to assess familial risk, if tumor test is HRRm-positive13,16,23,24

    Germline and somatic HRR mutations in patients with advanced prostate cancer are associated with shorter survival time than those without such mutations.4,5 As BRCA1/2 mutations in prostate cancer can be either germline or somatic, testing for both identifies all patients affected.

    Footnotes

    aTumor testing cannot distinguish between germline and somatic mutations.9 bGene panel testing was conducted in a large prospective study to identify the following genes in the DNA repair process: ATM, BRCA1, BRCA2, BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L.10

    ATM, ataxia-telangiectasia mutated; BRCA1/2, BReast CAncer susceptibility gene 1/2; CDK12, cyclin-dependent kinase 12; CHEK1/2, checkpoint kinase 1 and/or 2; CT, computed tomography; ctDNA, circulating tumor deoxyribonucleic acid; FANCL, fanconi anemia complementation group L; HRR, homologous recombination repair; mCRPC, metastatic castration-resistant prostate cancer; PALB2, partner and localizer of BRCA2; RAD51B/C/D, RAD51 paralog B, C and/or D; RAD54L, RAD54 paralog L; TRUS, transrectal ultrasound scan.

    Microscope icon

    Diagnostic Assays for HRR Mutations, Including BRCA1/2 Mutations

    Results can take between 7 to 21 days from receiving samples

    Tissue testing

    Laboratory and
    test name    		FDA approvalGenes or alterations
    assessed    		Minimum sample
    requirements    		Turnaround time

    Caris25-27

    Molecular Intelligence® Tumor
    Seek™ (NGS analysis)

    No

    HRRm (including BRCA1/2),
    dMMR, MSI

    FFPE block or 10 unstained
    slides (positively charged,
    unbaked) with a ≥20% tumor
    nuclei. Needle biopsy (4–6
    cores), FNA, malignant fluid
    cell block, and bone/bone
    metastasis are also
    acceptable

    ~10–14 days

    Foundation Medicine9,28,29

    FoundationOne® CDx

    Yes

    HRRm (including BRCA1/2),
    dMMR, MSI

    1 block + 1 H&E slide OR
    10 unstained slides (positively
    charged and unbaked at 4–5
    microns thick) + 1 H&E slide

    ≤12 days from receipt

    NeoGenomics30

    NeoTYPE® HRR Profile

    No

    		HRRm (including BRCA1/2)

    Paraffin block preferred

    14 days

    NeoGenomics31

    BRCA1/2 Mutations Analysis
    for Tumors

    No

    BRCA1/2

    Paraffin block is preferred OR
    1 H&E slide + 5–10 unstained
    slides (positively charged) cut
    at ≥5 microns

    14 days

    Tempus32-35

    Tempus xT
    (Solid tumor)

    No

    HRRm (BRCA1/2), dMMR,
    MSI

    FFPE block with a minimum
    of 20% tumor content

    9 days from receipt

    AstraZeneca is not affiliated with and does not control these websites. Inclusion of a website on AZPrecisionMed.com does not constitute endorsement of its content by the associated organizations. This document is intended as educational information and is not intended as a complete list of available testing options. AstraZeneca is not responsible for any test provider and does not endorse any particular diagnostic test. The accuracy and results of diagnostic tests vary, and AstraZeneca shall have no liability arising from such testing. Information provided herein should in no way be considered a guarantee of coverage, reimbursement, or patient assistance. Providers should contact third-party laboratories for information on their patient assistance programs. While diagnostic testing may assist providers in identifying appropriate treatment for patients, the decision and action should be decided by a provider in consultation with the patient. All products are trademarks of their respective holders, all rights reserved.

    BRCA1/2, BReast CAncer susceptibility gene 1/2; CDx, companion diagnostic; dMMR, deficient mismatch repair; DNA, deoxyribonucleic acid; FDA, US Food and Drug Administration; FFPE, formalin-fixed paraffin-embedded; FNA, fine needle aspiration; H&E, hematoxylin and eosin; HRRm, homologous recombination repair mutation; MSI, microsatellite instability.

    Plasma (ctDNA) testing

    Laboratory and
    test name    		FDA approvalGenes or alterations
    assessed    		Minimum sample
    requirements    		Turnaround time

    Foundation Medicine36-38

    FoundationOne®
    Liquid CDx

    Yes

    HRRm (including BRCA1/2), dMMR, MSI

    2 tubes of peripheral whole blood (8.5 mL per tube)

    ≤10 days from receipt

    Tempus39,40

    Tempus xF

    No

    2 Streck tubes of peripheral blood (8.5 mL per tube)

    7 days from receipt

    Guardant Health41,42

    Guardant360® CDx

    No

    HRRm (including BRCA1/2), dMMR

    ≥5 mL whole blood in Streck Cell-Free DNA BCT®

    7 days

    AstraZeneca is not affiliated with and does not control these websites. Inclusion of a website on AZPrecisionMed.com does not constitute endorsement of its content by the associated organizations. This document is intended as educational information and is not intended as a complete list of available testing options. AstraZeneca is not responsible for any test provider and does not endorse any particular diagnostic test. The accuracy and results of diagnostic tests vary, and AstraZeneca shall have no liability arising from such testing. Information provided herein should in no way be considered a guarantee of coverage, reimbursement, or patient assistance. Providers should contact third-party laboratories for information on their patient assistance programs. While diagnostic testing may assist providers in identifying appropriate treatment for patients, the decision and action should be decided by a provider in consultation with the patient. All products are trademarks of their respective holders, all rights reserved.

    BCT, blood collection tube; BRCA1/2, BReast CAncer susceptibility gene 1/2; CDx, companion diagnostic; ctDNA, circulating tumor deoxyribonucleic acid; dMMR, deficient mismatch repair; DNA, deoxyribonucleic acid; FDA, US Food and Drug Administration; HRRm, homologous recombination repair mutation; MSI, microsatellite instability.

    Germline testing

    Laboratory and
    test name    		FDA approvalGenes or alterations
    assessed    		Minimum sample
    requirements    		Turnaround time

    Ambry43-45

    Cancer Next®

    Yes

    3–4 mL whole blood, EDTA tube (purple top) or PAXgene® DNA tube (blue top) preferreda

    14–21 days

    GenPath46-48

    OnkoRisk™
    Oncology Management Panel

    No

    2–5 mL whole blood, lavender-top EDTA tube

    14 days

    GeneDx49,50

    OncoGene Dx: Hereditary
    Prostate Cancer Panel

    No

    HRRm (including BRCA1/2), dMMR

    2–5 mL blood, lavender-top tube

    2 weeks

    Invitae51,52

    Common Hereditary Cancers Panel

    No

    3 mL whole blood in a purple-top EDTA tube

    10–21 calendar days

    Invitae53,54

    Multi-Cancer Panel

    No

    3 mL whole blood in a purple-top EDTA tube

    10–21 calendar days

    Myriad55,56

    BRACAnalysis CDx® (BRCA1/BRCA2)

    Yes

    BRCA1/2

    ~7 mL peripheral whole blood in a BCT-containing EDTA

    <2 weeks

    Myriad57-59

    MyRisk® Hereditary Cancer

    No

    HRRm (including BRCA1/2), dMMR

    7 mL peripheral blood or buccal saliva sample

    ≤14 days

    Tempus xG33,60,61

    (powered by GeneDx) Common Hereditary Cancers

    No

    8 mL peripheral blood in a lavender-top EDTA tube or buccal saliva sample

    14–21 days from receipt

    AstraZeneca is not affiliated with and does not control these websites. Inclusion of a website on AZPrecisionMed.com does not constitute endorsement of its content by the associated organizations. This document is intended as educational information and is not intended as a complete list of available testing options. AstraZeneca is not responsible for any test provider and does not endorse any particular diagnostic test. The accuracy and results of diagnostic tests vary, and AstraZeneca shall have no liability arising from such testing. Information provided herein should in no way be considered a guarantee of coverage, reimbursement, or patient assistance. Providers should contact third-party laboratories for information on their patient assistance programs. While diagnostic testing may assist providers in identifying appropriate treatment for patients, the decision and action should be decided by a provider in consultation with the patient. All products are trademarks of their respective holders, all rights reserved.

    Footnotes

    aNGS sequencing panels and clinical exome sequencing require 6–10 mL.43

    BCT, blood collection tube; BRCA1/2, BReast CAncer susceptibility gene 1/2; CDx, companion diagnostic; dMMR, deficient mismatch repair; DNA, deoxyribonucleic acid; EDTA, ethylenediaminetetraacetic acid; FDA, US Food and Drug Administration; HRRm, homologous recombination repair mutation; NGS, next-generation sequencing.

    Browse a selection of major laboratories offering a range of biomarker testing options.

    Find a Testing Lab
    Scientist using a dropper adding solution to test tube

    This information is intended as educational and is not intended as a complete list of available testing options. AstraZeneca is not responsible for any test provider and does not endorse any particular diagnostic test. The accuracy and results of diagnostic tests vary, and AstraZeneca shall have no liability arising from such testing. Information provided herein should in no way be considered a guarantee of coverage, reimbursement, or patient assistance. Providers should contact third-party laboratories for information on their patient assistance programs. While diagnostic testing may assist providers in identifying appropriate treatment for patients, the decision and action should be decided by a provider in consultation with the patient. All products are trademarks of their respective holders, all rights reserved.

    DNA helix icon

    Interpreting and Reporting Biomarker Test Results

    HRRm testing aids in systemic treatment decisions, clinical trial enrollment, and/or genetic counseling on familial risk62

    Testing for HRRm, including BRCA1/2, may:

    • DNA helix icon

      Reveal patients who have an increased risk for hereditary cancers.63,64 Genetic counselors may be required to discuss germline testing in the pre-test setting, allowing patients to make informed decisions. Genetic counselors also play a key role in evaluating genetic testing results64

    • Diagnosis staging icon

      Offer prognostic insights on patients with metastatic prostate cancer and mutations in genes such as BRCA1/2 who are at risk for more aggressive disease and poorer outcomes4,65

    • Interpreting and Reporting Biomarker Test Results

      Provide predictive insights which aid in the development of a comprehensive treatment plan66,67

    • Actionable biomarkers icon

      Open opportunities for patients to be enrolled onto clinical trials to receive upcoming, biomarker-specific treatments62

    BRCA1/2, BReast CAncer susceptibility gene 1/2; HRRm, homologous recombination repair mutation.

    Key takeaway icon

    Considerations for Your Practice

    Consider HRRm status for treatment decision-making, clinical trial enrollment, and genetic counseling:

    • Test for HRRm at metastatic diagnosis
    • Re-evaluate HRR genes upon progression
    • Consider sample type and age when using tumor tissue for HRRm testing
    • Utilize plasma ctDNA testing for cases where tumor testing is not feasible
    • Explore solutions to common challenges you may face

    ctDNA, circulating tumor deoxyribonucleic acid; HRRm, homologous recombination repair mutation.

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    References

    1. Frey MK, Pothuri B. Gynecol Oncol Res Pract. 2017;4:4.
    2. Pilié P, et al. Nat Rev Clin Oncol. 2019;16(2):81–104.
    3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.4.2024. ©National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed May 17, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org
    4. Na R, et al. Eur Urol. 2017;71(5):740–747.
    5. Castro E, et al. J Clin Oncol. 2013;31(14):1748–1757.
    6. FDA. List of Cleared or Approved Companion Diagnostic Devices. Accessed Sept 30, 2024. https://​www.​fda.​gov/​medical-​devices/​in-​vitro-​diagnostics/​list-​cleared-​or-​approved-​companion-​diagnostic-​devices-​in-​vitro-​and-​imaging-​tools
    7. Shore N, et al. Future Oncol. 2021;17(22):2907–2921.
    8. Chung JH, et al. JCO Precis Oncol. 2019;3:PO.18.00283.
    9. Foundation Medicine. FoundationOne®. CDx Technical Information. Accessed Sept 30, 2024. https://​assets.​ctfassets.​net/​w98cd481qyp0/​41rJj28gFwtxCwHQxopaEb/​a01bc8565732f686d258757693d85ad2/​FoundationOne_​CDx_​Label_​Technical_​Info​.pdf
    10. de Bono J, et al. N Engl J Med. 2020;382(22):2091–2102.
    11. de Bono, et al. Presented at: ESMO Congress; September 27–October 1, 2019; Barcelona, Spain. Abstract 847PD.
    12. Lang SH, et al. Int J Oncol. 2019;55(3):597–616.
    13. Cheng HH, et al. J Natl Compr Canc Netw. 2019;17(5):515–521.
    14. Fiala C, Diamandis EP. BMC Med. 2018;16(1):166.
    15. Foundation Medicine. FoundationOne®. Liquid CDx. Accessed Sept 30, 2024. https://​assets.​ctfassets.​net/​w98cd481qyp0/​3a8jFw3KUjIU3RWPdcT9Ax/​dcb2ffd6d8d9a40a65ccf663269cc39a/​FoundationOne_Liquid_CDx_Label_Technical_Info​.pdf
    16. Wu H, et al. Gene Ther. 2017;24(10):601–609.
    17. Serefoglu EC, et al. Can Urol Assoc J. 2013;7(5-6):E293–E298.
    18. Friedlander TW, et al. Am Soc Clin Oncol Educ Book. 2017;37:358–369.
    19. Sailer V, et al. Cancer. 2018;124(5):1008–1015.
    20. Chang Y, et al. Ther Clin Risk Manag. 2017;13:1363–1374.
    21. Merker J, et al. J Clin Oncol. 2018;36(16):1631–1641.
    22. Cimadamore A, et al. Int J Mol Sci. 2021;22(11):1–15.
    23. National Institutes of Health. What is a Gene Variant and How do Variants Occur? Accessed Sept 30, 2024. https://​medlineplus​.gov/​genetics/​understanding/​mutationsanddisorders/​genemutation/
    24. BRACAnalysis CDx® Technical Information. Accessed Sept 30, 2024. https://​s3​.amazonaws​.com/​myriad-web/​BRACAnalysisCDxTS.pdf
    25. Caris. Comprehensive Tumor Profiling. Accessed Sept 30, 2024. https://www.carislifesciences.com/products-and-services/molecular-profiling/testing-menu
    26. Caris. Tissue Profiling. Accessed Sept 30, 2024. https://www.carislifesciences.com/products-and-services/molecular-profiling/tissue-profiling/
    27. Caris. Tumor Profiling Requisition. Accessed Sept 30, 2024. https://www.carislifesciences.com/wp-content/uploads/2021/08/TN0034-v19_Tumor_Req_eForm.pdf
    28. Foundation Medicine. Our Testing Portfolio. Accessed Sept 30, 2024. https://www.foundationmedicine.com/portfolio
    29. FoundationOne®. CDx. Specimen Instructions. Accessed Sept 30, 2024. https://​www.​foundationmedicine​.com/​sites/​default/​files/​document/​FoundationOneHeme_FFPE_Specimen_Instructions.pdf
    30. NeoGenomics. NeoTYPE® HRR Profile. Accessed Sept 30, 2024. https://​neogenomics​.com/​test-menu/​neotyper-hrr-profile
    31. NeoGenomics. BRCA1/2 Mutation Analysis for Tumors. Accessed Sept 30, 2024. https://neogenomics.com/test-menu/brca12-mutation-analysis-tumors
    32. Tempus. xT Gene Panel. Accessed Sept 30, 2024. https://www.tempus.com/wp-content/uploads/2023/06/Tempus_xT-Gene-Panel-NYS.pdf
    33. Tempus. Specimen Guidelines for Providers. Accessed Sept 30, 2024. https://www.tempus.com/wp-content/uploads/2024/11/Tempus-Onco_Specimen-Guidelines.pdf
    34. Tempus. xT Solid Tumor. Accessed Sept 30, 2024. https://www.tempus.com/oncology/genomic-profiling/xt-xr
    35. Tempus. xT (v3) Validation. Accessed Sept 30, 2024. https://www.tempus.com/wp-content/uploads/2020/02/xTv3-Validation_010920-1.pdf
    36. Foundation Medicine. FoundationOne® Liquid CDx. Prostate Profiler. Accessed Sept 30, 2024. https://​www​.foundationmedicine.com​/sites​/default​/files​/document​/Prostate_Profiler.pdf
    37. Foundation Medicine. FoundationOne® Liquid CDx. Accessed Sept 30, 2024. https://www.foundationmedicine.com/test/foundationone-liquid-cdx
    38. Foundation Medicine. FoundationOne® Liquid CDx. Product Features. Accessed Sept 30, 2024. https://​www​.foundationmedicine.com​/sites​/default​/files​/document​/F1LCDx_SS.pdf
    39. Tempus. xF Gene Panel. Accessed Sept 30, 2024. https://www.tempus.com/wp-content/uploads/2022/09/Tempus-xF_Gene-Panel.pdf
    40. Tempus. xF Liquid Biopsy. Accessed Sept 30, 2024. https://www.tempus.com/oncology/genomic-profiling/xf
    41. Guardant360®. CDx. Technical Information. Accessed Sept 30, 2024. https://www.guardantcomplete.com/assets/pdf/Guardant360-CDx-Technical-Information-US.pdf
    42. Guardant360®. CDx. Specification Sheet. Accessed Sept 30, 2024. https://guardanthealth.eu/wp-content/uploads/2021/01/G360-Specification-Sheet-1.pdf
    43. Ambry Genetics®. Specimen requirements. Accessed Sept 30, 2024. https://www.ambrygen.com/providers/specimen-requirements
    44. Ambry Genetics®. CancerNext®. Accessed November 28, 2024. https://www.ambrygen.com/providers/oncology/test-menu
    45. Ambry Genetics®. Cancer Test Requisition Form (Abbreviated). Accessed Sept 30, 2024. https://www.ambrygen.com/file/material/view/2052/Cancer%20Test%20Requisition%20Form%20%28Abbreviated%29%20%2819081_0%29.pdf
    46. GenPath. OnkoRiskTM Test Options. Accessed Sept 30, 2024. https://www.genpathdiagnostics.com/hcp/oncology/hereditary-cancer-testing/hereditary-cancer-testing-options/#toggle-id-1-closed
    47. GenPath. OnkoRiskTM Specimen Requirements. Accessed Sept 30, 2024. https://www.genpathdiagnostics.com/hcp/oncology/hereditary-cancer-testing/specimen-requirements/
    48. GenPath. OnkoriskTM Hereditary Cancer Program. Accessed Sept 30, 2024. https://www.genpathdiagnostics.com/hcp/oncology/hereditary-cancer-testing
    49. GeneDx. Test Information Sheet. Accessed Sept 30, 2024. https://providers.genedx.com/Resources/TIS-Files/TIS-J665.pdf
    50. GeneDx. Hereditary Prostate Cancer Panel. Accessed Sept 30, 2024. https://providers.genedx.com/tests/detail/hereditary-prostate-cancer-panel-875
    51. Invitae Common Hereditary Cancers Panel. Clinical Description. Accessed Sept 30, 2024. https://view.publitas.com/invitae-byeex67v6jpk/invitae-common-hereditary-cancers-panel-clinical-description/page/1
    52. Invitae. Invitae Common Hereditary Cancers Panel. Accessed Sept 30, 2024. https://www.invitae.com/en/providers/test-catalog/test-01102
    53. Invitae. Multi-Cancer Panel. Clinical Description. Accessed Sept 30, 2024. https://www.invitae.com/us/providers/test-catalog/test-01101
    54. Invitae. Multi-Cancer Panel. Accessed Sept 30, 2024. https://www.invitae.com/en/providers/test-catalog/test-01101
    55. Center for Drug Evaluation and Research. Summary of Safety and Effectiveness Data (SSED). Accessed Sept 30, 2024. https://​www​.accessdata​.fda​.gov/​drugsatfda_docs/nda/​2014/206162Orig1s000OtherR.pdf
    56. Myriad Genetics. BRACAnalysis CDx®. Accessed Sept 30, 2024. https://myriad-oncology.com/bracanalysiscdx
    57. Myriad Genetics. MyRisk® Hereditary Cancer Technical Specifications. Accessed Sept 30, 2024. https://s3.amazonaws.com/myriad-library/technical-specifications/myRisk+Hereditary+Cancer+Tech+Specs.pdf
    58. Myriad Genetics. MyRisk® Hereditary Cancer Test. Accessed Sept 30, 2024. https://myriad.com/genetic-tests/myrisk-germline-test
    59. Myriad Genetics. Test Submission Checklist for Hereditary Cancer Syndromes. Accessed Sept 30, 2024. https://​myriad-web​.s3​.amazonaws​.com/​myRisk/​Test​BSubmission​BChecklist_AUG2012​.pdf
    60. Tempus. xG. Hereditary Cancer Panels. Accessed Sept 30, 2024. https://www.tempus.com/wp-content/uploads/2022/09/Tempus-xG_Overview.pdf
    61. Tempus. xG/xG+. Hereditary Cancer Germline Testing. Accessed Sept 30, 2024. https://www.tempus.com/oncology/genomic-profiling/xg
    62. Gonzalez D, et al. J Pathol Clin Res. 2021;7(4):311–325.
    63. Cucchiara V, et al. Eur Urol. 2018;73(4):572–582.
    64. Russo J and Veda NG. Nat Rev Urol. 2022;19:331.
    65. Heeke AL, et al. JCO Precis Oncol. 2018;2018:PO.17.00286.
    66. Tan D, et al. J Clin Oncol. 2008;26(34):5530–5536.
    67. Pellegrino B, et al. ESMO Open. 2019;4(2):e000480.

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