Hereditary Breast and Ovarian Cancer syndrome, Lynch syndrome, Familial Adenomatous Polyposis, von Hippel Thus, although recognizing the rationale for widespread population screening, the panel recommends that universal testing for founder BRCA1/2 mutations in individuals of Ashkenazi Jewish ancestry, regardless of personal or family history, be offered primarily in the setting of longitudinal research studies. Participation in clinical trials is especially encouraged. Cancer genetic risk assessment and genetic counseling is a multistep process involving the identification and counseling of individuals at risk for familial or hereditary cancer. Multi-gene panel testing is when someone undergoes genetic testing for more than one or two genes. Jaiswal S, Fontanillas P, Flannick J, . Berliner JL, Fay AM, Cummings SA, . Jones S, Hruban RH, Kamiyama M, . Accessed February 28, 2020. Couch FJ, Johnson MR, Rabe KG, . Concerns about underutilization of genetic testing have spurred interest in broader peri-diagnostic testing. J Clin Oncol 2019;37:1070–1080. Thus, one should be mindful that, when testing unaffected individuals (in the absence of having tested affected family members), significant limitations may exist in interpreting the test results, and testing multiple family members may be indicated, because absence of a mutation in one unaffected relative does not rule out a mutation in others. Also, gene tests can assess for small changes, such as an altered chemical "step" within the DNA "ladder," called gene mutations. The new NCCN guidelines indicate that genetic counseling and testing should be considered for all men with high-risk, very high-risk, regional, or metastatic prostate cancer. There is now strong evidence that genes beyond BRCA1/2 confer markedly increased risk of breast and/or ovarian cancers, such as CDH1, PALB2, PTEN, and TP53. These patients should be considered for referral to research studies that aim to define the functional impact of the gene variant, such as variant reclassification programs through clinical laboratories or registries. Multigene panels to evaluate hereditary cancer risk: reckless or relevant? J Clin Oncol 2016;34:4186–4187. Swisher EM, Lin KK, Oza AM, . Slater EP, Langer P, Niemczyk E, . 4. Front Physiol 2014;5:70. For most families in whom the presence of a pathogenic or likely pathogenic variant is unknown, it is best to consider testing an affected family member first, especially a family member with early-onset disease, bilateral disease, or multiple primaries, because that individual has the highest likelihood of a positive test result. The guidelines have also strengthened recommendations around somatic (tumor tissue) testing. The considerable rate of resectable asymptomatic lesions found through routine screening of high-risk individuals demonstrates the potential for downstaging (ie, identification of lesions at an earlier stage). Patel MR, Eppolito AL, Willingham FF. There is also an increase in the chance of finding genotypically distinct cell lines (ie, genetic mosaicism) with next-generation sequencing.43 Clones of noncancerous cells (ie, aberrant clonal expansion) containing a pathogenic TP53 variant have been found in healthy adults undergoing multigene testing. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. Genet Med 2015;17:51–57. JAMA Oncol 2016;2:723–724. The complete and most recent version of these NCCN Guidelines is available free of charge at NCCN.org. Cragun D, Radford C, Dolinsky JS, . UAN: JA4008196-0000-20-005-H01-P. All clinicians completing this activity will be issued a certificate of participation. This activity is supported by an independent educational grant from Merck & Co., Inc. Advances in cancer genetics, such as increased use of multigene panel testing, has transformed the clinical approach to testing at-risk patients and their families. J Clin Oncol 2016;34:4071–4078. © National Comprehensive Cancer Network, Inc. 2020. He also discussed what needs to be addressed in the future to further increase knowledge of genetic testing and improve its use. Proc Natl Acad Sci USA 2014;111:14205–14210. Therefore, germline testing for PRSS1, SPINK1, and other genes associated with pancreatitis is generally not recommended unless the individual’s personal or family history is suggestive of hereditary pancreatitis.85 Pancreas cancer screening is recommended in individuals harboring one of these variants only in the presence of a clinical phenotype consistent with hereditary pancreatitis. J Natl Cancer Inst 2018;110:714–725. Humphris JL, Johns AL, Simpson SH, . Renaux-Petel M, Charbonnier F, Théry JC, . Charles Bankhead is … Cancer Discov 2012;2:41–46. The most recent Genetic/Familial High-Risk Assessment: Breast and Ovarian NCCN guidelines has a new section on multi-gene genetic testing. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. Lucas AL, Shakya R, Lipsyc MD, . Hong YC, Liu HM, Chen PS, . CA Cancer J Clin 2012;62:118–128. Deleterious germline mutations are a risk factor for neoplastic progression among high-risk individuals undergoing pancreatic surveillance. Genet Med 2017;19:754–762. Clin Genet 2014;86:510–520. High prevalence of BRCA1 and BRCA2 germline mutations with loss of heterozygosity in a series of resected pancreatic adenocarcinoma and other neoplastic lesions. Multi-gene panel testing is when someone undergoes genetic testing for more than one or two genes. Syngal S, Brand RE, Church JM, . In these cases, the unaffected individual or unaffected close relative with the highest likelihood of testing positive for the pathogenic or likely pathogenic variant should be tested. Hasan A, Moscoso DI, Kastrinos F. The role of genetics in pancreatitis. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Contribution of de novo and mosaic TP53 mutations to Li-Fraumeni syndrome. In addition, studies have shown that genetic testing based on clinical guidelines emphasizing a family history of breast, ovarian, prostate, or other cancers missed approximately 38% to 56% of mutation carriers with Ashkenazi Jewish ancestry,1,2,4,5 providing some evidence to support population-based genetic testing among the Ashkenazi Jewish population. The updated NCCN "Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic" are available from the NCCN website. J Med Genet 2018;55:173–180. In that case, the genetic testing laboratory can limit the search for pathogenic or likely pathogenic variants in additional family members to the same location in the gene. J Community Genet 2015;6:351–359. Cragun D, Camperlengo L, Robinson E, . Genet Med 2018;20:1515–1521. Current NCCN Recommendations for Prostate Cancer Genetic Testing – Summary: James L. Mohler, MD, discusses the rationale and development of the 2019 NCCN guideline recommendations on genetic testing for prostate cancer. N Engl J Med 2019;381:317–327. This activity is supported by a medical education grant from Exelixis, Inc. However, the panel raised concerns about the demand on genetic counseling resources, the preparedness of healthcare professionals to provide cancer genetic counseling and management, and participants’ fears and concerns about testing, including those regarding privacy, stigmatization, and the need for appropriate medical and/or surgical management in patients and family members found to have a founder mutation. ... along with genetic counseling. Recently, there has been an increase in genetic test results through direct-to-consumer (DTC) services or through tumor profiling. Hair follicle: a reliable source of recipient origin after allogeneic hematopoietic stem cell transplantation. Katz SJ, Ward KC, Hamilton AS, . There is also the potential for impact on mortality rates, although long-term studies are needed in this area. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 2018;379:753–763. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meeting. Testing of second-degree relatives may be considered in select cases. Lancet Oncol 2019;20:636–648. When it is not feasible to test the affected relative first, then the Genet Med 2018;20:809–816. Given that mortality rates for this cancer are high,77,78 it may be beneficial to family members to test patients near the time of diagnosis, because the option to test the patient may not be available for very long. Genet Med 2014;16:407–412. When screening is recommended, it may be performed with contrast-enhanced MRI/MRCP and/or endoscopic ultrasound.80,81,87 MRI and endoscopic ultrasound have been shown to be superior in detecting subcentimeter pancreatic cysts compared with CT.87 Screening at a high-volume center of expertise and in the context of a research study is preferred. Kari B. Wisinski, MD, Panel Member, has disclosed that she has received honoraria from Genomic Health, Inc., and grant/research support from Pfizer Inc. Matthew B. Yurgelun, MD, Panel Member, has disclosed that he has received consulting fees from and is a scientific advisor for Janssen. NCCN guidelines now recommend germline and somatic tumor testing in specific clinical scenarios due to treatment and family implications. Given the considerable rate of predisposing mutations in patients with pancreatic cancer, as well as the fact that typical clinical factors (eg, young age of onset, family history of cancer) are poorly predictive for identifying mutation carriers, universal genetic testing for these individuals is warranted (see CRIT-3, page 384). Reports regarding germline findings that may impact medical management should come from laboratories that are certified by the College of American Pathologists (CAP) and CLIA, with some US states (eg, New York) having additional reporting requirements. Hall MJ, Obeid E, Daly MB. This activity is supported in part by an educational grant from Bayer Healthcare Pharmaceuticals. J Natl Compr Canc Netw 2014;12:1339–1346. Integrate into professional practice the updates to the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Describe the rationale behind the decision-making process for developing the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2, Population testing for cancer predisposing BRCA1/BRCA2 mutations in the Ashkenazi-Jewish community: a randomized controlled trial, A pragmatic testing-eligibility framework for population mutation screening: the example of BRCA1/2, A comparison of the detection of BRCA mutation carriers through the provision of Jewish population-based genetic testing compared with clinic-based genetic testing, Population screening for BRCA1/BRCA2 founder mutations in Ashkenazi Jews: proactive recruitment compared with self-referral, Olaparib for metastatic breast cancer in patients with a germline BRCA mutation, Talazoparib in patients with advanced breast cancer and a germline BRCA mutation, Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial, Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation, Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial, Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer, Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial, Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial, Society of Gynecologic Oncology statement on risk assessment for inherited gynecologic cancer predispositions, Hair follicle: a reliable source of recipient origin after allogeneic hematopoietic stem cell transplantation, Differentiation of human bone marrow-derived cells into buccal epithelial cells in vivo: a molecular analytical study, Somatic TP53 variants frequently confound germ-line testing results, Conflicting interpretation of genetic variants and cancer risk by commercial laboratories as assessed by the prospective registry of multiplex testing, Comparison of locus-specific databases for BRCA1 and BRCA2 variants reveals disparity in variant classification within and among databases, Consistency of BRCA1 and BRCA2 variant classifications among clinical diagnostic laboratories, BRCA1 and BRCA2 genetic testing-pitfalls and recommendations for managing variants of uncertain clinical significance, Third party interpretation of raw genetic data: an ethical exploration, False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care, American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility, ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing, Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer, Clinical evaluation of a multiple-gene sequencing panel for hereditary cancer risk assessment, Uptake, results, and outcomes of germline multiple-gene sequencing after diagnosis of breast cancer, Gene panel testing for inherited cancer risk. Individuals Who Provided Content Development and/or Authorship Assistance: Testing Criteria for High-Penetrance Breast and/or Ovarian Cancer Susceptibility Genes, Evaluating the Source of Genetic Testing Information, NCCN CATEGORIES OF EVIDENCE AND CONSENSUS, NCCN.org/disclosures/guidelinepanellisting.aspx, https://www.eeoc.gov/laws/statutes/gina.cfm. Germline BRCA mutations in a large clinic-based cohort of patients with pancreatic adenocarcinoma. Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2. Salo-Mullen EE, O’Reilly EM, Kelsen DP, . Uptake, results, and outcomes of germline multiple-gene sequencing after diagnosis of breast cancer. Lancet Oncol 2020;21:162–174. Next-generation sequencing for inherited breast cancer risk: counseling through the complexity. Updates include an expansion of genetic testing criteria to take into account other genes besides BRCA1/2 that are associated with an increased risk of breast and/or ovarian cancer, streamlined organization of these testing criteria, revisions to testing criteria related to Ashkenazi Jewish ancestry, genetic testing for the purpose of systemic therapy decision-making, an increased focus on phenotypically directed multigene panel tests, and the addition of information regarding pancreas screening and genes with associated pancreatic cancer. These companies do not provide comprehensive genetic analysis that includes gross deletion or duplication analysis. Mary B. Daly, MD, PhD, Panel Chair, has disclosed that she has no relevant financial relationships. JAMA 2006;295:1379–1388. Clin Cancer Res 2013;19:3396–3403. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma. Pre-test genetic counseling services for hereditary breast and ovarian cancer delivered by non-genetics professionals in the state of Florida. Metcalfe KA, Poll A, Royer R, . These scenarios include identification of a pathogenic or likely pathogenic variant; negative results despite family history suggestive of inherited disease; VUS result for which a provider considers altering clinical management; mosaic or possibly mosaic result; discrepant interpretation of variants (eg, discordant results across laboratories); for interpretation of polygenic risk scores (ie, relative risk for disease, compared with the genomes of other individuals); and detection of pathogenic or likely pathogenic variants from DTC testing. Genet Med 2013;15:565–574. J Clin Oncol 2015;33:3124–3129. It’s important for all pancreatic cancer patients to explore genetic testing with their healthcare teams. Thats according to new guidelines established by the National Comprehensive Cancer Network (NCCN), a group of 27 expert cancer centers throughout the U.S. that provides recommendations called Clinical Practice Guidelines for the treatment of some 30 different cancer types. Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. Gut 2020;69:7–17. Differentiation of human bone marrow-derived cells into buccal epithelial cells in vivo: a molecular analytical study. Clinical and pathologic features of familial pancreatic cancer. The “BRCA1/2 Testing Criteria” page has been expanded to “Testing Criteria for High-Penetrance Breast and/or Ovarian Cancer Susceptibility Genes” (see CRIT-1 and CRIT-2, above and page 383, respectively). Tung N, Battelli C, Allen B, . Genetic testing should be considered in individuals for whom there is a personal or family history suggesting susceptibility to hereditary cancer and for whom results can potentially impact risk management and treatment. Some examples of these programs and registries include ClinVar (the archival database at the National Center for Biotechnology Information), the NIH-funded Clinical Genome Resource (ClinGen), the Clinical Cancer Genomics Community Research Network of the United States, Mexico, and South America (CCGCRN), Prospective Registry of Multiplex Testing (PROMPT), the international Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), and the International Society for Gastrointestinal Hereditary Tumours (InSiGHT). In these cases, phenotype-directed testing based on personal and family history through a multigene panel test may be more efficient and/or cost-effective.29–31 Multigene testing may also be considered for individuals who tested negative for one particular syndrome but whose personal and family history is suggestive of an inherited susceptibility.29,32 Panel members indicated that it has become routine practice at their institutions to order phenotypically directed multigene panel tests to assess for pathogenic changes in multiple relevant genes simultaneously (see GENE-1, page 385). Kaufman B, Shapira-Frommer R, Schmutzler RK, . Genetic Information Nondiscrimination Act of 2008. Multigene tests also increase the likelihood of detecting a VUS.27–29,34,40–42 However, as multigene testing is increasingly used, the frequency of a variant being interpreted as a VUS is expected to decrease. Vasen H, Ibrahim I, Ponce CG, . J Natl Cancer Inst 2014;107:379. Balmaña J, Digiovanni L, Gaddam P, . If you have any questions, please e-mail education@nccn.org. Tran SD, Pillemer SR, Dutra A, . Pancreatic cancer is thought to have a familial or hereditary component in approximately 10% of cases.56–60 Harboring a pathogenic or likely pathogenic variant has been found to be associated with a greater incidence of pancreatic cancer than family history alone (without the presence of an associated germline variant).61 Germline mutations commonly found in pancreatic adenocarcinoma include BRCA1, BRCA2, CDKN2A, mismatch repair genes associated with Lynch syndrome (MSH2, MLH1, MSH6, PMS2, EPCAM), ATM, PALB2, STK11, and TP53.57,58,61–71 BRCA2 and CDKN2A are generally the most prevalent, with rates in moderate- to high-risk families ranging from 2% to 6% for BRCA2 and 1.5% to 2.5% for CDKN2A.58,59,72,73 In addition, hereditary pancreatitis, which is associated with a significantly increased risk for pancreatic cancer, is associated with the genes PRSS1 and SPINK1.57 Patients with pancreatic cancer and Ashkenazi Jewish ancestry may have a greater likelihood of testing positive for a BRCA1/2 mutation, with prevalence of detected mutations in this group ranging from 5.5% to 19%, and mutations more common for BRCA2.69,71,74,75. Genet Med 2019;21:213–223. National Comprehensive Cancer Network® (NCCN®) Criteria* Genetic testing for the following syndromes is medically necessary when an individual meets the testing criteria outlined in the relevant NCCN® Clinical Practice Guidelines in Oncology (NCCN Guideline®), (Gastric Cancer, v2.2018; Genetic/Familial High-Risk Assessment: Colorectal, v1.2018; Chaffee KG, Oberg AL, McWilliams RR, . While BRCA1 and BRCA2 have received much attention as they are linked to 20% to 25% of hereditary breast cancers and 5% to 10% of all breast cancers, 6 genetic testing has expanded to include 28 genes. Genetic counselors can be a good referral source, should there be a need for genetic testing. Available at: Risk assessment and genetic counseling for hereditary breast and ovarian cancer: recommendations of the National Society of Genetic Counselors, Genetic testing for cancer susceptibility, NSGC practice guideline: risk assessment and genetic counseling for hereditary breast and ovarian cancer, Shared genetic susceptibility to breast cancer, brain tumors, and Fanconi anemia, Differences in BRCA counseling and testing practices based on ordering provider type, Gaps in receipt of clinically indicated genetic counseling after diagnosis of breast cancer, Pre-test genetic counseling services for hereditary breast and ovarian cancer delivered by non-genetics professionals in the state of Florida, Projecting the supply and demand for certified genetic counselors: a workforce study, Clinical and pathologic features of familial pancreatic cancer, Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer, Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history, Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer, Deleterious germline mutations are a risk factor for neoplastic progression among high-risk individuals undergoing pancreatic surveillance, Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma, ATM mutations in patients with hereditary pancreatic cancer, PALB2 mutations in European familial pancreatic cancer families, Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene, Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer, Prevalence of pathogenic mutations in cancer predisposition genes among pancreatic cancer patients, Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms, Identification of germline genetic mutations in patients with pancreatic cancer, Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer, Germline BRCA mutations in a large clinic-based cohort of patients with pancreatic adenocarcinoma, The prevalence of BRCA2 mutations in familial pancreatic cancer, BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study, BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma, High prevalence of BRCA1 and BRCA2 germline mutations with loss of heterozygosity in a series of resected pancreatic adenocarcinoma and other neoplastic lesions, Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds, Cancers with increasing incidence trends in the United States: 1999 through 2008, Benefit of surveillance for pancreatic cancer in high-risk individuals: outcome of long-term prospective follow-up studies from three European expert centers, Risk of neoplastic progression in individuals at high risk for pancreatic cancer undergoing long-term surveillance, Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium, ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes, Pancreatic cancer risk in hereditary pancreatitis, Hereditary pancreatitis for the endoscopist, Frequent detection of pancreatic lesions in asymptomatic high-risk individuals, Disclosure of Relevant Financial Relationships. Selection of appropriate candidates for genetic testing is based on the personal and familial characteristics that determine the individual’s prior probability of being a carrier of a pathogenic or likely pathogenic variant, and on their psychosocial degree of readiness to receive genetic test results. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. For individuals potentially meeting established criteria for ≥1 hereditary cancer syndrome(s), genetic testing should be considered along with appropriate pretest and posttest counseling. Therap Adv Gastroenterol 2013;6:169–179. Gynecol Oncol 2015;136:3–7. Furthermore, the personal and/or family history criteria included may suggest the possibility of additional syndromes and would necessitate additional unlisted genes to be evaluated. For the 2020 update, the panel expanded the guidelines to include a focus on pancreatic cancer, including the addition of a new section on pancreas screening and genes associated with pancreatic cancer. Based on these rapid advances, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Genetic/Familial High-Risk Assessment: Breast and Ovarian (now Breast, Ovarian, and Pancreatic) have undergone some major revisions for the 2020 update. Canto MI, Almario JA, Schulick RD, . © 2019-2020 National Comprehensive Cancer Network. Medicine (ACCME): NCCN designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit™. The integration of next-generation sequencing panels in the clinical cancer genetics practice: an institutional experience. Factors that limit the informativeness of the pedigree are small family size, a small number of individuals of the susceptible sex for sex-limited cancers, reduced penetrance, early deaths in family members (which precludes the possibility that they will develop adult diseases), prophylactic surgeries that remove an organ from subsequent risk for cancer (eg, hysterectomy for uterine fibroids in which the ovaries are also removed), adoptions, and inaccurate or incomplete information on family members (eg, in the case of adoption or divorce).48,49 It is also important to know the ancestry/ethnicity of the individual, because members of certain groups (eg, Ashkenazi Jewish) have increased risks of carrying pathogenic or likely pathogenic variants for specific diseases. N Engl J Med 2014;371:2488–2498. Green RC, Berg JS, Grody WW, . Hu C, Hart SN, Polley EC, . Gene panel testing for inherited cancer risk. Clin Genet 2015;87:473–477. Genovese G, Kähler AK, Handsaker RE, . Robert Pilarski, MS, LGC, Panel Vice Chair, has disclosed that he has no relevant financial relationships. Lancet Oncol 2018;19:975–986. Accessed February 28, 2020. Curr Oncol Rep 2014;16:371. Genetic testing for hereditary cancer susceptibility is medically necessary when all of the following criteria are met: • Genetic testing results will impact medical management • National Comprehensive Cancer Network Guidelines™ (NCCN GUIDELINES ®) include category 1, 2A, or 2B and/or other published management recommendations for an