Accurate and Timely BRCA Mutation Testing Can Help Inform Treatment Decisions1,2

Biomarker testing is a multistep process.

Choose a sample type icon
CHOOSE a sample type

Tumor tissue or blood samples can be used to detect BRCA mutations; patients who are BRCA mutation-positive through tissue testing should be tested for a germline mutation.3-6

Blood samples

  • Detect germline BRCA mutations6
  • Inform familial risk4
  • Can inform treatment decisions7

Tumor samples

Tumor samples

  • Detect germline and somatic BRCA mutations but does not distinguish between them3
  • Must be followed with blood sample testing to determine familial risk4,6
  • Must be followed with blood sample testing to inform treatment decisions4,6,7

According to NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®):

  • Confirmatory germline mutation testing is recommended if a BRCA mutation is found while testing a tumor sample8
  • Germline BRCA mutation testing is recommended for patients with HER2–negative mBC to determine eligibility for targeted treatment9

Germline BRCA mutations can provide information about familial risk and determine eligibility for treating certain types of mBC with targeted therapy3,4,7

Collect the sample icon breast cancer
COLLECT the sample

The quantity of DNA analyzed can affect the accuracy of the results; therefore, sufficient sample must be collected.10

Blood samples11

  • Draw sufficient whole blood sample to allow for testing
  • For example: BRACAnalysis CDx® requires collection of ≈7 mL of whole blood in a tube containing EDTA (provided in the sample collection kit)
Process the sample icon
PROCESS the sample

If necessary, samples should be processed quickly and according to specific test instructions to preserve DNA quality.1,10

Blood samples11

  • Refer to test instructions; processing often is not required
  • For example: BRACAnalysis CDx® requests shipping the whole blood sample to the testing lab at ambient temperatures
Choose a diagnostic test icon
CHOOSE a diagnostic test

Diagnostic tests may use different technologies, such as Sanger sequencing or next-generation sequencing (NGS).

Sanger sequencing

Advantages

  • Gold standard12
  • Highly accurate12

Considerations

  • Tests a limited amount of DNA at one time12
  • Should be supplemented with PCR to detect all types of BRCA mutations5

NGS

Advantages

  • Used in panel testing to sequence large amounts of DNA in parallel12
  • More accurately identifies a positive result13

Considerations

  • More accurately identifies unknown variants that are not actionable and, therefore, require more extensive pre-test counseling14
  • Must be chosen carefully, because panels may test different genes and have a different way of classifying variants8

To optimize turnaround time and cost efficiency, some laboratories offer testing for BRCA mutations first, then automatically reflex to a larger multigene panel if the BRCA mutation test returns negative results.14

An FDA-approved test is available to detect BRCA mutations in BC7

An FDA-approved test is available to detect BRCA mutations in BC7

 
  BRACAnalysis CDx®15
  • Testing technology
  • PCR and Sanger Sequencing
  • Sample type
  • Whole blood
  • Mutation type
  • Germline

BRACAnalysis CDx®15

Testing technology

PCR and Sanger sequencing

Sample type

Whole blood

Mutation type

Germline

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Find more information about BRACAnalysis CDx®

CLIA-certified LDTs are available to detect BRCA mutations

CLIA-certified LDTs are available to detect BRCA mutations

Ambry Genetics®19-21

Testing technology

NGS

Sample type

Blood, saliva, buccal swab, or tissue

Mutation type

Germline or somatic (tissue testing cannot distinguish between germline and somatic)

ARUP® Laboratories22,23

Testing technology

PCR and Sanger sequencing

Sample type

Whole blood

Mutation type

Germline

GeneDx24

Testing technology

NGS

Sample type

Blood or buccal swab

Mutation type

Germline

Invitae25

Testing technology

NGS

Sample type

Whole blood or saliva

Mutation type

Germline

LabCorp26,27

Testing technology

NGS

Sample type

Whole blood or saliva

Mutation type

Germline

Quest DiagnosticsTM28,29

Testing technology

NGS

Sample type

Whole blood

Mutation type

Germline

Kew, Inc.30-33,†

Testing technology

NGS

Sample type

FFPE tissue

Mutation type

Somatic and germline (but does not distinguish between them)

 
  Ambry Genetics®19-21 
 ARUP® Laboratories22,23 
 GeneDx24 
 Invitae25
 LabCorp26,27 Quest DiagnosticsTM28,29 Kew, Inc.30-33,†
  • Testing technology
  • NGS
  • PCR and Sanger sequencing
  • NGS
  • NGS
  • NGS
  • NGS
  • NGS
  • Sample type
  • Blood, saliva, buccal swab, or tissue
  • Whole blood
  • Blood or buccal swab
  • Whole blood or saliva
  • Whole blood or saliva
  • Whole blood
  • FFPE tissue
  • Mutation type
  • Germline or somatic (tissue testing cannot distinguish between germline and somatic)
  • Germline
  • Germline
  • Germline
  • Germline
  • Germline
  • Somatic and germline (but does not distinguish between them)

Laboratory-developed tests (LDTs) are diagnostic tests that are developed and used within a single laboratory. Although not FDA-approved, they meet specific requirements of and are regulated by the Clinical Laboratory Improvement Amendments (CLIA) of 1988.16,17,*

*These tests are performed in laboratories that adhere to performance specifications established by the Clinical Laboratory Improvement Amendments (CLIA) of 1988 under the regulation of the Centers for Medicare & Medicaid Services. They are not FDA approved.16,18

†Kew, Inc., is CLIA-certified in all states except New York.

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Find more LDTs, along with contact information for the testing laboratories.

LDTs are not the same as direct-to-consumer commercial tests34

Direct-to-consumer tests have varying levels of evidence to support their claims, and few have been reviewed by the FDA.34 Therefore, care must be taken when interpreting results from direct-to-consumer tests.34

Appropriate sample collection, processing, and testing are key in determining BRCA mutation status and making informed treatment decisions.1,2

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Learn about interpreting BRCA mutation test results

BRCA, breast cancer susceptibility gene; CLIA, Clinical Laboratory Improvement Amendments; EDTA, ethylenediaminetetraacetic acid; FDA, Food and Drug Administration; FFPE, formalin-fixed paraffin-embedded; HER2, human epidermal growth factor receptor 2; LDT, laboratory-developed test; mBC, metastatic breast cancer; NCCN, National Comprehensive Cancer Network; NGS, next-generation sequencing; PCR, polymerase chain reaction.

 

References: 1. Leyland-Jones BR et al. J Clin Oncol. 2008;26(34):5638-5644. 2. Smith KL et al. Cancer J. 2011;17(6):492-499. 3. Robson ME et al. J Clin Oncol. 2015;33(31):3660-3667. 4. George A et al. Nat Rev Clin Oncol. 2017;14(5):284-296. 5. Wallace AJ. Eur J Hum Genet. 2016;24(suppl 1):S10-S18. 6. Robson ME et al; American Society of Clinical Oncology. J Clin Oncol. 2010;28(5):893-901. 7. Food and Drug Administration (FDA). https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm. Accessed September 5, 2018. 8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic V1.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed March 3, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V3.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed March 16, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 10. Capoluongo E et al. Semin Oncol. 2017;44(3):187-197. 11. Center for Drug Evaluation and Research; Food and Drug Administration (FDA). https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000OtherR.pdf. Accessed October 26, 2018. 12. Rizzo JM, Buck MJ. Cancer Prev Res (Phila). 2012;5(7):887-900. 13. O’Leary E et al. Ann Surg Oncol. 2017;24(10):3060-3066. 14. Stanislaw C et al. Cancer Biol Med. 2016;13(1):55-67. 15. BRACAnalysis CDx® [technical information]. Salt Lake City, UT: Myriad Genetics Laboratories, Inc.; 2017. 16. Fitzgibbons PL et al; College of American Pathologists Pathology and Laboratory Quality Center. Arch Pathol Lab Med. 2014;138(11):1432-1443. 17. FDA. https://www.fda.gov/medicaldevices/productsandmedicalprocedures/invitrodiagnostics/laboratorydevelopedtests/default.htm. Updated October 12, 2018. Accessed October 26, 2018. 18. Centers for Medicare & Medicaid Services (CMS). https://www.cms.gov/Regulations-and-Guidance/Legislation/CLIA/index.html?redirect=/clia. Updated September 19, 2018. Accessed October 26, 2018. 19. CMS. https://www.ambrygen.com/file/material/view/759/CLIA_EXP_5.29.20.pdf. Effective May 30, 2018. Accessed October 26, 2018. 20. Ambry Genetics®. https://www.ambrygen.com/clinician/genetic-testing/23/oncology/brca1-and-brca2. Accessed October 26, 2018. 21. Ambry Genetics®. https://www.ambrygen.com/clinician/specimen-requirements. Accessed October 26, 2018. 22. ARUP® Laboratories. https://www.aruplab.com/testing/licensure-accreditations. Accessed May 23, 2019. 23. ARUP® Laboratories. http://ltd.aruplab.com/tests/pub/2011954. Accessed May 23, 2019. 24. GeneDx. https://www.genedx.com/test-catalog/medical-specialty/oncology. Accessed May 23, 2019. 25. Invitae. https://www.invitae.com/en/physician/tests/50002/#info-panel-assay_information. Accessed May 23, 2019. 26. Labcorp. https://www.labcorp.com/sites/default/files/LabCorp_Phoenix%2C%20AZ_CLIA_03D0528350_Expires20210208.pdf. Accessed May 23, 2019. 27. Labcorp. https://www.labcorp.com/test-menu/21366/brca12-comprehensive-analysis-brcassure%C2%AE. Accessed May 23, 2019. 28. Quest DiagnosticsTM. http://www.questvantage.com/wp-content/uploads/2014/06/25654_SB3428_BRCAvantage_Oncologist_Brochure_V2_MT_060914.pdf. Accessed May 23, 2019. 29. Quest DiagnosticsTM. https://www.questdiagnostics.com/home/about/locations/licenses-accreditations. Accessed May 23, 2019. 30. Kew, Inc. https://kewinc.com/kew-inc/. Accessed May 23, 2019. 31. Kew, Inc. https://kewinc.com/wp-content/uploads/2017/07/Full-gene-list.pdf. Accessed May 23, 2019. 32. Kew, Inc. https://kewinc.com/wp-content/uploads/2017/07/Specimen-Handling-Instructions.pdf. Accessed May 23, 2019. 33. Kew, Inc. https://kewinc.com/kews-cancerplex-molecular-diagnostic-test-made-available-cancer-patients-eu-mytomorrows-platform/. Accessed May 23, 2019. 34. FDA. https://www.fda.gov/medical-devices/vitro-diagnostics/direct-consumer-tests. Updated November 1, 2018. Accessed May 23, 2019.

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