nccn guidelines genetic testing

For individuals potentially meeting established criteria for ≥1 hereditary cancer syndrome(s), genetic testing should be considered along with appropriate pretest and posttest counseling. Robson M, Im SA, Senkus E, . Eur J Hum Genet 2017;25:1189–1194. 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. Mary A. Dwyer, MS, CGC, Director, Guidelines Operations, NCCN, has disclosed that she has no relevant financial relationships. Badalato L, Kalokairinou L, Borry P. Third party interpretation of raw genetic data: an ethical exploration. Gut 2020;69:7–17. N Engl J Med 2017;377:523–533. Myra J. Wick, MD, PhD, Panel Member, has disclosed that she has no relevant financial relationships. Risk assessment and genetic counseling for hereditary breast and ovarian cancer: recommendations of the National Society of Genetic Counselors. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Klein AP, Brune KA, Petersen GM, . JAMA Oncol 2018;4:1066–1072. Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history. N Engl J Med 2014;371:2477–2487. Accessed February 28, 2020. Canto MI, Almario JA, Schulick RD, . Another analysis of 354 asymptomatic high-risk individuals showed suspicious pancreas lesions in 19% who were screened.80 Of the lesions detected through screening, 90% were resectable, and the 3-year overall survival rate was 85% in those with resectable lesions. Semin Oncol 2016;43:548–553. 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. Ancillary testing of nonlymphoid noncancerous tissue can be used to help determine the true presence of a germline variant.17. BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma. Cancer 2015;121:4382–4388. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical Upon completion of this activity, participants will be able to: The NCCN staff listed below discloses no relevant financial relationships: Kerrin M. Rosenthal, MA; Kimberly Callan, MS; Genevieve Emberger Hartzman, MA; Erin Hesler; Kristina M. Gregory, RN, MSN, OCN; Rashmi Kumar, PhD; Karen Kanefield; and Kathy Smith. Gastroenterology 2018;155:740–751.e2. Fibroblasts are also indicated when testing individuals with active or recent hematologic malignancies.17, A counseling dilemma is posed by the finding of a variant of unknown significance (VUS), a genetic alteration that may actually represent a benign polymorphism unrelated to an increased cancer risk or may indicate an increased cancer risk. This phenomenon can often be attributed to clonal hematopoiesis, a condition in which a hematopoietic stem cell begins making blood cells with the same acquired mutation.17 When there is no evidence of a hematologic malignancy, then it is referred to as clonal hematopoiesis of indeterminate potential (CHIP). 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. Comparison of locus-specific databases for BRCA1 and BRCA2 variants reveals disparity in variant classification within and among databases. Panel-based testing for inherited colorectal cancer: a descriptive study of clinical testing performed by a US laboratory. 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. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of NCCN . Cancer Epidemiol Biomarkers Prev 2019;28:293–302. Identification of germline genetic mutations in patients with pancreatic cancer. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic Version 1.2020 contains several updates including new and expanded sections on risk assessment and management related to three major cancer types, while also maintaining a more conservative approach toward testing practices where the evidence is still lacking. These revisions include reorganization of the guidelines by disease and syndrome type; inclusion of criteria for high-penetrance genes associated with breast and ovarian cancer beyond BRCA1/2; the addition of pancreatic cancer to the title, with new information added about pancreas screening and genes associated with pancreatic cancer; clarification of testing indications for the purpose of systemic therapy decision-making; and new recommendations for testing of people with Ashkenazi Jewish ancestry. Multigene panel testing detects equal rates of pathogenic BRCA1/2 mutations and has a higher diagnostic yield compared with limited BRCA1/2 analysis alone in patients at risk for hereditary breast cancer. Kaufman B, Shapira-Frommer R, Schmutzler RK, . ATM mutations in patients with hereditary pancreatic cancer. Gene tests assess either one gene or a short piece of DNA. Tumor profiling can be considered complementary to germline testing. Genet Med 2018;20:119–127. Mary B. Daly, MD, PhD, Panel Chair, has disclosed that she has no relevant financial relationships. Balmaña J, Digiovanni L, Gaddam P, . There is also the potential for impact on mortality rates, although long-term studies are needed in this area. Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate. N Engl J Med 2018;379:753–763. All rights reserved. © 2019-2020 National Comprehensive Cancer Network. Benefit of surveillance for pancreatic cancer in high-risk individuals: outcome of long-term prospective follow-up studies from three European expert centers. The integration of next-generation sequencing panels in the clinical cancer genetics practice: an institutional experience. Multiple genes have been identified that are associated with breast cancer. Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. The second revision of note is regarding testing with the intent to aid in systemic therapy decision-making. ... along with genetic counseling. These NCCN Guidelines Insights summarize the panel’s discussion and most recent recommendations regarding criteria for high-penetrance genes associated with breast and ovarian cancer beyond BRCA1/2, pancreas screening and genes associated with pancreatic cancer, genetic testing for the purpose of systemic therapy decision-making, and testing for people with Ashkenazi Jewish ancestry. All recommendations are category 2A unless otherwise noted. Curr Oncol Rep 2014;16:371. N Engl J Med 2019;381:317–327. 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. J Clin Oncol 2018;36:1218–1224. Hall MJ, Obeid E, Daly MB. In an interview with Targeted Oncology during the 2019 Prostate Cancer Consensus Conference, James L. Mohler, MD, explained the reasons for changes to the NCCN guidelines on genetic testing and counseling in prostate cancer. Differentiation of human bone marrow-derived cells into buccal epithelial cells in vivo: a molecular analytical study. 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. 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. Concerns about underutilization of genetic testing have spurred interest in broader peri-diagnostic testing. Multi-Gene Testing (GENE-1) The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. If there is no access to longitudinal studies, then testing may be offered when pretest and posttest genetic counseling are available. Major discussion topics this year included multigene testing, risk management recommendations for less common genetic mutations, and salpingectomy for ovarian cancer risk reduction. Kurian AW, Ward KC, Hamilton AS, . Carriers should be encouraged to recontact their genetics providers every few years for updates, because laboratories may issue amended reports as the knowledge base surrounding hereditary cancer risk expands. © 2021 MJH Life Sciences™ and Contemporary OB/GYN. These NCCN Guidelines Insights summarize the panel’s discussion and most recent recommendations regarding criteria for high-penetrance genes associated with breast and ovarian cancer beyond BRCA1/2, pancreas screening and genes associated with pancreatic cancer, genetic testing for the purpose of systemic therapy decision-making, and testing for people with Ashkenazi Jewish ancestry. As a result of the above, NCCN recommends that genetic counseling and testing be offered to All individuals with exocrine pancreatic cancer First degree relatives of individuals diagnosed with exocrine pancreatic cancer Genes that will likely be ordered include BRCA1/2, as well as ATM, CDKN2A, STK11, TP53 and most Lynch syndrome genes These agents include olaparib6 and talazoparib7 for HER2-negative metastatic breast cancer; niraparib,8 olaparib,9 and rucaparib10 for chemotherapy-refractory ovarian cancer; and olaparib as a maintenance therapy option for metastatic pancreatic cancer.11 Some studies investigating PARP inhibitors in patients who have germline BRCA1/2 mutations with metastatic castration-resistant prostate cancer are promising.12,13 Even though management of breast, ovarian, and/or pancreatic cancer risk in individuals with associated hereditary syndromes continues to be the focus of these NCCN Guidelines, they now identify intent to aid in systemic therapy decision-making as a scenario in which germline testing is clinically indicated. Continuing pharmacy education credit is reported to the CPE Monitor once you have completed the posttest and evaluation and claimed your credits. If you have any questions, please e-mail education@nccn.org. Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate. 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. Cancer Epidemiol Biomarkers Prev 2007;16:342–346. First, Ashkenazi Jewish ancestry without a personal cancer history is now included as a scenario for which genetic testing may be considered. Holter S, Borgida A, Dodd A, . Testing typically used by companies providing ancestry information directly to consumers is microarray-based single-nucleotide polymorphism (SNP) testing that has not been validated for clinical use. Vail PJ, Morris B, van Kan A, . In addition to the errors inherent in working with raw uncurated data from DTC laboratories, other limitations of these services include inadequate informed consent processes, clinical validity and utility, and medical oversight.22 An analysis of concordance between DTC and confirmatory test results for 49 patients showed a false-positive rate of 40%, as well as variant classification errors in 8 patients.23 Given the limitations of the information obtained from DTC services, confirmatory germline testing by a certified laboratory is recommended, and changes to a patient’s medical management based solely on DTC testing results are not recommended.23. Cancer Epidemiol Biomarkers Prev 2016;25:207–211. 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. Blazer KR, Slavin T, Weitzel JN. Cancer Res 2011;71:2222–2229. Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. Hereditary pancreatitis for the endoscopist. The NCCN Guidelines Insights highlight important changes in the NCCN Guidelines recommendations from previous versions. Casadei S, Norquist BM, Walsh T, . Shared genetic susceptibility to breast cancer, brain tumors, and Fanconi anemia. This activity is supported in part by an educational grant from Bayer Healthcare Pharmaceuticals. Available at: https://www.eeoc.gov/laws/statutes/gina.cfm. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. Routine use of gene panel testing in hereditary breast cancer should be performed with caution. These NCCN Guidelines Insights summarize some of the recent revisions made to the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. © 2021 MJH Life Sciences and Contemporary OB/GYN. Cancers with increasing incidence trends in the United States: 1999 through 2008. False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care. Uptake, results, and outcomes of germline multiple-gene sequencing after diagnosis of breast cancer. Vasen H, Ibrahim I, Ponce CG, . The NCCN Guidelines Insights do not represent the full NCCN Guidelines; further, the National Comprehensive Cancer Network® (NCCN®) makes no representations or warranties of any kind regarding their content, use, or application of the NCCN Guidelines and NCCN Guidelines Insights and disclaims any responsibility for their application or use in any way. Tumor testing tends to be designed to address treatment actionability and prognosis.24 Therefore, a variant interpreted as pathogenic or likely pathogenic in the germline may be interpreted as normal or as a VUS in the tumor, if that variant has no clear clinical implications. BRCA1 and BRCA2 genetic testing-pitfalls and recommendations for managing variants of uncertain clinical significance. Clin Genet 2010;78:490–494. Nursing (ANCC): NCCN designates this educational activity for a maximum of 1.0 contact hour. Familial pancreatic cancer. Goggins M, Overbeek KA, Brand R, . Ann Surg Oncol 2015;22:3282–3288. Medicine (ACCME): NCCN designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit™. In such cases, DNA of the individual being tested should be extracted from a fibroblast culture, if available. Hair follicle: a reliable source of recipient origin after allogeneic hematopoietic stem cell transplantation. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. Proc Natl Acad Sci USA 2010;107:12629–12633. This may include the relative closest to the family member with the youngest age at diagnosis, bilateral disease, multiple primary tumors, or other cancers associated with a suspected hereditary syndrome. Tung N, Battelli C, Allen B, . Offit K, Levran O, Mullaney B, . The purpose of cancer genetic counseling is to educate individuals about the genetic, biologic, and environmental factors related to a cancer diagnosis and/or risk for disease to help them derive personal meaning from cancer genetic information, and to empower them to make educated, informed decisions about genetic testing, cancer screening, and cancer prevention. Lancet Oncol 2019;20:636–648. Zhen DB, Rabe KG, Gallinger S, . 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). 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. Walsh T, Lee MK, Casadei S, . Ferrone CR, Levine DA, Tang LH, . The testing criteria listed are for breast and/or ovarian cancer susceptibility genes with strong or moderate evidence of actionability (eg, BRCA1/2, CDH1, and PALB2; testing criteria for Li-Fraumeni syndrome and Cowden syndrome continue to be presented in their own dedicated sections). Also, gene tests can assess for small changes, such as an altered chemical "step" within the DNA "ladder," called gene mutations. Genet Med 2018;20:809–816. If the inline PDF is not rendering correctly, you can download the PDF file here. Almost 25% of women with breast cancer have a family history of the disease, and women with an affected first-degree relative have a 1.75-fold higher risk of developing cancer.1 That risk increases to 2.5-fold with two or more affected first-degree relatives. Patel MR, Eppolito AL, Willingham FF. Deleterious germline mutations are a risk factor for neoplastic progression among high-risk individuals undergoing pancreatic surveillance. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. A pragmatic testing-eligibility framework for population mutation screening: the example of BRCA1/2. Trepanier A, Ahrens M, McKinnon W, . He can be reached at DrLockwood@ubm.com. Swisher EM, Lin KK, Oza AM, . Genet Med 2015;17:51–57. The NCCN Guidelines are a statement of consensus of the authors regarding their views of currently accepted approaches to cancer treatment. Counselling framework for moderate-penetrance cancer-susceptibility mutations. 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. Gynecol Oncol 2015;136:3–7. Genetic Information Nondiscrimination Act of 2008. J Community Genet 2015;6:351–359. Therap Adv Gastroenterol 2013;6:169–179. Science 2009;324:217. Age-related CHIP is associated with increased risk of hematologic malignancies,44,45 but may also lead to unnecessary clinical intervention. He also discussed what needs to be addressed in the future to further increase knowledge of genetic testing and improve its use. J Natl Compr Canc Netw 2014;12:1339–1346. Robson ME, Bradbury AR, Arun B, . It is important to note that there may be inconsistencies in how programs and registries interpret the clinical actionability of some VUS, which may lead to confusion regarding medical management.18–20 Clinicians and scientists should work together to develop a VUS classification system as more information is discovered in research studies.21. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. There are several issues to consider regarding multigene testing. Clin Cancer Res 2013;19:3396–3403. Bone Marrow Transplant 2007;40:871–874. Population screening for BRCA1/BRCA2 founder mutations in Ashkenazi Jews: proactive recruitment compared with self-referral. Katz SJ, Ward KC, Hamilton AS, . to save searches and organize your favorite content. Recently, there has been an increase in genetic test results through direct-to-consumer (DTC) services or through tumor profiling. Clin Genet 2015;87:473–477. Robert Pilarski, MS, LGC, Panel Vice Chair, has disclosed that he has no relevant financial relationships. We evaluated surgeon adherence to NCCN guidelines and studied … Posttest counseling includes disclosure of results, a discussion of the associated medical risks, an assessment of the impact of the results on the individual’s emotional state, a discussion of the impact of the results on the medical management of the individual, and determination of how and where the patient will be screened for cancer risk.14 Counseling should include information on any available resources, such as disease-specific support groups, high-risk clinics, advocacy groups, and research studies.50 Probands should be advised regarding possible inherited cancer risk to relatives and available options for risk assessment and management. 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. These tests look for extra gene copies (duplicated or amplified genes), missing genes (gene deletions), or incorrectly placed genes (translocated genes). Age-related clonal hematopoiesis associated with adverse outcomes. The tumor is included in NCCN Guidelines® without 1 or 2A NCCN® recommendations for molecular testing for the specific tumor type The requested genetic variant or profile is correlated with a known therapy, but that therapy We evaluated surgeon adherence to NCCN guidelines and studied patterns of testing in newly diagnosed BC patients. Kapoor NS, Curcio LD, Blakemore CA, . Germline genetic testing is now recommended for all patients with pancreatic adenocarcinoma (the most common form of pancreatic cancer), according to updated guidelines released this week by the National Comprehensive Cancer Network (NCCN). Participation in clinical trials is especially encouraged. March 22, 2019. Cancer Res 2004;64:2634–2638. Genetic testing in PCa patients may inform prognosis, treatment options, and have implications for family counseling. This activity is supported by a medical education grant from Exelixis, Inc. Tung N, Domchek SM, Stadler Z, . 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. Some NCCN treatment guidelines for BRCA-related cancers now recommend treatment with PARP inhibitors for patients with germline or somatic BRCA1/2 mutations, because PARP inhibitors have been shown to be active in these patients. Next-generation sequencing for inherited breast cancer risk: counseling through the complexity. Third-party services are available to assist patients with interpreting their raw data, but these services are not government-regulated. Charles Bankhead is … Pancreatic cancer risk in hereditary pancreatitis. Nat Rev Clin Oncol 2016;13:581–588. J Genet Couns 2007;16:241–260. In support of improving patient care, National Comprehensive Cancer Network (NCCN) is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Berliner JL, Fay AM. J Clin Oncol 2019;37:1070–1080. Counselors should recommend genetic counseling and testing for at-risk relatives. 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). Differences in BRCA counseling and testing practices based on ordering provider type. However, during the meeting for the 2020 update, the panel acknowledged that most genetic testing is conducted by providers with limited expertise in genetics, and often without pretest genetic counseling.52–54 Shortages in genetics health providers,55 expansion of testing indications, and increased accessibility of testing due to plummeting costs, inclusive of DTC models for testing, provided the impetus for the panel to identify scenarios in which referral to a genetics health provider should be considered. Contribution of de novo and mosaic TP53 mutations to Li-Fraumeni syndrome. Accessed February 28, 2020. Pharmacists: You must complete the posttest and evaluation within 30 days of the activity. 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; Cancer 2015;121:25–33. Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms. Gaps in receipt of clinically indicated genetic counseling after diagnosis of breast cancer. J Natl Cancer Inst 2018;110:1067–1074. Given the elevated rates of pathogenic or likely pathogenic variants in pancreatic cancer and that pancreatic cancer risk increases when there is a family history,76 testing of first-degree relatives of patients may be beneficial. Cancer Discov 2012;2:41–46. 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 help providers identify appropriate candidates for counseling and testing. The updated NCCN "Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic" are available from the NCCN website. Salo-Mullen EE, O’Reilly EM, Kelsen DP, . Cancer 2014;120:3669–3675. Multigene panels to evaluate hereditary cancer risk: reckless or relevant? JAMA 2006;295:1379–1388. Prior to the version 1.2020 update, these NCCN Guidelines focused largely on testing criteria for BRCA1/2 and appropriate risk management for carriers of a BRCA1 or BRCA2 pathogenic or likely pathogenic variant. Testing of second-degree relatives may be considered in select cases. Multigene panels to evaluate hereditary cancer risk: reckless or relevant? If this is not possible, buccal cells may be considered as an alternative source for DNA15; however, one study reported that over time, buccal epithelial cells are replaced by donor-derived cells in allogeneic HSCT recipients.16 Therefore, genetic testing using buccal swab samples may be limited given this known risk of donor DNA contamination. 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. Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. 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. Lowery MA, Wong W, Jordan EJ, . Cost-effectiveness of population-based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 mutation testing in unselected general population women, Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing, Next-generation sequencing for inherited breast cancer risk: counseling through the complexity, Increased reach of genetic cancer risk assessment as a tool for precision management of hereditary breast cancer, Counselling framework for moderate-penetrance cancer-susceptibility mutations, Routine use of gene panel testing in hereditary breast cancer should be performed with caution, Panel-based testing for inherited colorectal cancer: a descriptive study of clinical testing performed by a US laboratory, Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients, The integration of next-generation sequencing panels in the clinical cancer genetics practice: an institutional experience, Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel, Multigene panel testing detects equal rates of pathogenic BRCA1/2 mutations and has a higher diagnostic yield compared with limited BRCA1/2 analysis alone in patients at risk for hereditary breast cancer, Age-related clonal hematopoiesis associated with adverse outcomes, Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence, Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors, Genetic Information Nondiscrimination Act of 2008. .

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