Hereditary Cancer Screening

Understand the value of screening beyond BRCA1 & BRCA2

We believe that no one should find out they have a gene mutation that increases their risk for cancer, by being diagnosed with cancer. Learn why multigene screening identifies more opportunities for cancer risk reduction in those with a strong family history of cancer.

Reliant Value

Reliant Value

How do Reliant panels enable more patients that meet criteria to get ahead of cancer?

Society Guidelines

Do professional societies recognize the utility of multigene hereditary cancer screening?

Analytic Validity

Can Reliant accurately detect whether a specific genetic variant is present or absent?

Clinical Validity

Are the genetic variants analyzed by Reliant associated with an increased risk for cancer?

Clinical Utility

Does Reliant provide information that leads to interventions and improved outcomes?

Counsyl Reliant™ Cancer Screen Value

Our thoughtful panel design and clinical rigor allow for more comprehensive identification and opportunities for better management among clinically appropriate patients, compared to single-gene testing. We provide support to providers and patients before and after screening; from identifying clinically appropriate patients to ensuring patients understand their result via our genetic counseling services.

Population with Established Medical Necessity

Reliant is appropriate for use in individuals meeting National Comprehensive Cancer Network (“NCCN”) criteria based on a personal or family history suggestive of a hereditary cancer syndrome.

Clinically Actionable Results

Reliant panels are focused on genes associated with high or moderate lifetime cancer risks and all have management guidelines developed by NCCN and other professional societies.

Support at Every Step

Automated tools help to identify high-risk patients, deliver pre-test education, and provide post-test genetic counseling. These tools aid patients and providers throughout the hereditary cancer screening process.

When ordering Reliant, providers may choose the appropriate tumor-specific panel, depending on the patient’s risk factors.

Breast/Gyn Panel
Includes 19 genes associated with breast, ovarian, endometrial, and other gynecological cancers.

Gastrointestinal Panel
Includes 17 genes associated with gastric, colorectal, and other gastrointestinal cancers.

Comprehensive Panel
Includes 29 genes associated with breast, gynecological, gastrointestinal, prostate, thyroid, melanoma and other cancers.

Multigene screening is more comprehensive and efficient than single-syndrome testing

While BRCA1 and BRCA2 account for a large percentage of hereditary breast cancer, variants in several other genes can also increase lifetime breast cancer risk.  These genes also have established management guidelines.2-9

Lifetime breast cancer risk for genes commonly tested on multigene panels

Created with Sketch.
*Providers are recommended to discuss risk-reducing mastectomy.

Mutations in genes other than BRCA1 and BRCA2 account for 50% of hereditary breast cancer.10

Due to variable penetrance and overlap, it can be difficult to differentiate cancer syndromes based on personal or family history alone. This family’s PALB2 mutation would have been missed if testing were limited to BRCA1 and BRCA2 .12

 

Analytic Validity

Can Reliant accurately detect whether a specific genetic variant is present or absent?

Our CLIA-certified, CAP-accredited, NYS-permitted clinical genomics laboratory is among the most automated and advanced in the world, allowing for reduced costs and rapid turnaround times. Our next generation sequencing platform is scientifically validated, with >99.99% sensitivity, specificity, and accuracy.18

Clinical Validity

Are the variants analyzed by Reliant associated with a hereditary cancer syndrome?

Each gene on the Reliant Cancer Screen has an established association for at least one type of cancer.19

Variant Curation

A Critical Measure of Clinical Validity
Curation refers to classification of novel variants as pathogenic, benign, or unknown. Counsyl has developed a robust curation program that is 99% concordant with public databases and other laboratories that share variant data publically.20 The variant curation team is made up of 30 expert variant curators with over 120 years of combined curation experience.

Variants of Uncertain Significance (VUS)
VUS have been cited as a limitation of hereditary cancer panels. Importantly, it is recommended that patients with VUS be managed just as patients with negative results, i.e. based on their personal and family history.21  This important management information is included in Reliant reports.

Clinical Utility

Does Reliant provide information that leads to interventions and improves outcomes?

Interventions, such as increased surveillance and prophylactic surgery, have demonstrated a reduction in cancer morbidity and mortality for well-established syndromes, such as hereditary breast and ovarian cancer (HBOC) and Lynch syndrome.22-25

Interventions are proven to reduce risk

Surgical Interventions

90%

Breast cancer risk

Bilateral Mastectomy for women with hereditary breast cancer
96%

Ovarian cancer risk

Bilateral Salpingo Oophorectomy for women with hereditary ovarian cancer

High Risk Screening

23%

Breast cancer mortality

When MRI is added to screening protocol
63%

Colon cancer mortality

With colonoscopy every 1-2 years in individuals with Lynch syndrome"

Greater than 90% of positive results from multigene panels impact clinical management when limited to genes with management guidelines and performed in patients with qualifying personal and family history.26

Guideline based management of more recently discovered syndromes with risks similar to those of HBOC and Lynch syndrome is expected to result in similar reductions in cancer risk, as well as morbidity and mortality.27,28

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References

  1. Data on file, Counsyl.
  2. Petrucelli N, et al. BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.” 1998 (Updated 2013). In: GeneReviews® [Internet]. Pagon RA, Adam MP, Ardinger HH, et al., ed. (Seattle, WA: University of Washington, Seattle; 1993-2015).
  3. Schneider K, et al. Li-Fraumeni Syndrome. 1999 (Updated 2013). In: GeneReviews® [Internet]. Pagon RA, Adam MP, Ardinger HH, et al., ed. (Seattle, WA: University of Washington, Seattle; 1993-2015).
  4. Eng C. PTEN Hamartoma Tumor Syndrome. 2001 (Updated 2014). In: GeneReviews® [Internet]. Pagon RA, Adam MP, Ardinger HH, et al., ed. (Seattle, WA: University of Washington, Seattle; 1993-2015).
  5. McGarrity TJ, et al. Peutz-Jeghers Syndrome. 2001 (Updated 2013). In: GeneReviews® [Internet]. Pagon RA, Adam MP, Ardinger HH, et al., ed. (Seattle, WA: University of Washington, Seattle; 1993-2015).
  6. Antoniou AC, et al. 2014. Breast-cancer risk in families with mutations in PALB2. N Engl J Med 371:497-506.
  7. Van der Post RS, et al. 2015. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet 52:361-74. PMID: 25979631.
  8. National Institutes of Health (NIH)/National Cancer Institute. Breast Cancer Risk in American Women. http://www.cancer.gov/types/breast/risk-fact-sheet (accessed 2018).
  9. Saslow D, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75-89. PMID: 17392385.
  10. Kapoor N, et al. 2015. Multigene panel testing detects equal rates of pathogenic BRCA1/2 mutations and has a higher diagnostic yield compared to limited BRCA1/2 analysis alone in patients at risk for hereditary breast cancer. Ann Surg Oncol 22, 3282–3288
  11. Southey MC, et al. 2010. A PALB2 Mutation Associated with High Risk of Breast Cancer. Breast Cancer Res 12:R109. PMID: 21182766.
  12. National Society of Genetic Counselors. Position Statements: “Use of Multi-Gene Panel Tests.” 2017. https://www.nsgc.org/p/bl/et/blogaid=870 (accessed 6/27/2018).
  13. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) “Genetic/Familial High-Risk Assessment: Breast and Ovarian” Version 1.2018.
  14. The American Society of Breast Surgeons. “Consensus Guideline on Hereditary Genetic Testing for Patients With and Without Breast Cancer.” 2017. https://www.breastsurgeons.org/new_layout/about/statements/PDF_Statements/BRCA_Testing.pdf (accessed 2018).
  15. Society of Gynecological Oncology. “SGO Clinical Practice Statement: Next Generation Cancer Gene Panels Versus Gene by Gene Testing.” https://www.sgo.org/clinical-practice/guidelines/next-generation-cancer-gene-panels-versus-gene-by-gene-testing/ (accessed 2018).
  16. The American College of Obstetricians and Gynecologists (ACOG)/Society of Gynecological Oncology. “ACOG Practice Guidelines: Clinical Management Guidelines for Obstetrician–Gynecologists.” 2017;182. https://www.sgo.org/wp-content/uploads/2012/09/PB-182.pdf (accessed 2018).
  17. Robson ME, et al. 2015. “American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility.” J Clin Oncol. 2015;33:3660–7. PMID: 26324357.
  18. Vysotskaia VS, et al. 2017. Development and validation of a 36-gene sequencing assay for hereditary cancer risk assessment. PeerJ 5:e3046. PMID: 28243543.
  19. Price KS, et al. 2018. Inherited Cancer in the Age of Next-Generation Sequencing. Biol Res Nurs 20:192-204. PMID: 29325452.
  20. Castiblanco J, et al. Validation of internal laboratory variant classifications using ClinVar. AMP Annual Meeting, 2016, Charlotte, NC. 2016. Poster.
  21. Easton DF, et al. 2007. A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes. Am J Hum Genet. 2007;81:873-83. PMID: 17924331.
  22. Hartmann LC, et al. 1999. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 340:77-84. PMID: 9887158.
  23. Rebbeck TR, et al. 2002. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 346:1616-22. PMID: 12023993.
  24. Plevritis SK, et al. 2006. Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging. JAMA 295:2374-84. PMID: 16720823.
  25. De Jong AE, et al. 2006. Decrease in mortality in Lynch syndrome families because of surveillance. Gastroenterology 130:665-71. PMID: 16530507.
  26. Rosenthal ET, et al. 2015. Outcomes of clinical testing for 76,000 patients utilizing a panel of 25 genes associated with increased risk for breast, ovarian, colorectal, endometrial, gastric, pancreatic, melanoma and prostate cancers. Scientific poster presented at the American Society for Clinical Oncology Annual Meeting in Chicago, IL.
  27. O’Leary E, et al. 2017. Expanded Gene Panel Use for Women With Breast Cancer: Identification and Intervention Beyond Breast Cancer Risk. Ann Surg Oncol 24:3060-6. PMID: 28766213.
  28. Kurian AW, et al. 2014. Clinical evaluation of a multiple-gene sequencing panel for hereditary cancer risk assessment. J Clin Oncol 32:2001-9. PMID: 24733792.
  29. Desmond A, et al. 2015. Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment. JAMA Oncol 1, 943–951.
  30. Ricker, C. et al. 2016. Increased yield of actionable mutations using multi-gene panels to assess hereditary cancer susceptibility in an ethnically diverse clinical cohort. 209, 130–137.
  31. Gupta S, et al. NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 3.2017. J. Natl. Compr. Canc. Netw. 15, 1465–1475 (2017).
  32. Li Y, et al. 2017. A Multigene Test Could Cost-Effectively Help Extend Life Expectancy for Women at Risk of Hereditary Breast Cancer. Value in Health 20 (4): 547–55.
  33. Gallego C, et al. Next-Generation Sequencing Panels for the Diagnosis of Colorectal Cancer and Polyposis Syndromes: A Cost-Effectiveness Analysis. J. Clin. Oncol. 33, 2084–2091 (2015).
  34. Richards S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17, 405–424 (2015).