Medical Guidelines

NCCN® Clinical Practice Guidelines

  • Breast Cancer

    NCCN Guidelines® – Breast Cancer

    “Consider multigene assay to assess prognosis and determine chemotherapy benefit.”

    EndoPredict receives Category 2A Evidence and Consensus for both node-negative and node-positive patients (1-3 nodes).

    National Comprehensive Cancer Network® Clinical Practice Guidelines in Oncology (NCCN Guidelines®) – Breast Cancer. Version 4.2020.

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  • Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic Cancer

    NCCN Guidelines® – Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic Cancer

    Moving beyond BRCA 1/2, NCCN® expands testing criteria for high penetrance genes.

    “Consider comprehensive testing of patient with multi-gene panel… Testing Criteria for high-penetrance breast and/or ovarian cancer susceptibility genes… often includes BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53 among others.”

    National Comprehensive Cancer Network® Clinical Practice Guidelines in Oncology (NCCN Guidelines®) – Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic Cancer Version 1.2020 – December 4, 2019.

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  • Pancreatic Cancer

    NCCN Guidelines® – Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic Cancer

    NCCN® recommends all Pancreatic Cancer patients should receive genetic testing.

    “Recommend genetic counseling and germline testing for all individuals diagnosed with exocrine Pancreatic Cancer [and] first-degree relatives of individuals diagnosed with exocrine Pancreatic Cancer.”

    National Comprehensive Cancer Network® Clinical Practice Guidelines in Oncology (NCCN Guidelines®) – Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic Cancer Version 1.2020 – December 4, 2019.

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  • Prostate Cancer

    NCCN Guidelines® – Prostate Cancer

    Prognostic information independent of NCCN or CAPRA risk groups.

    “Men with low- or favorable intermediate-risk disease and life expectancy of greater or equal to 10 years may consider the use of the following tumor-based molecular assays: Decipher, Oncotype DX Prostate, Prolaris, and ProMark. Men with unfavorable intermediate- and high-risk disease and life expectancy greater than or equal to 10 years may consider the use of Decipher and Prolaris tumor-based molecular assays. Retrospective studies have shown that molecular assays performed on prostate biopsy or radical prostatectomy (RP) specimens provide prognostic information independent of NCCN or CAPRA risk groups.”

    National Comprehensive Cancer Network® Clinical Practice Guidelines in Oncology (NCCN Guidelines®) – Prostate Cancer Version 2.2020.

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    NCCN® elevates its germline testing reference to RECOMMENDED for all Prostate Cancer risk groups. The endorsement includes gathering family history and genetic information for germline variants from a panel of genes.

    “…genetic testing for germline variants should include MLH1, MSH2, MSH6, and PMS2 (for Lynch syndrome) and homologous recombination genes BRCA1, BRCA2, ATM, PALB2, and CHEK2.”

    National Comprehensive Cancer Network® Clinical Practice Guidelines in Oncology (NCCN Guidelines®) – Prostate Cancer Version 1.2019 – March 6, 2019.

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Professional Society Statements

Lab Accuracy

  • American College of Medical Genetics and Genomics (ACMG)

    ACMG Guidelines are not a definitive variant classification program and “following” the guidelines does not quantify a lab’s interpretive accuracy.

    “[L]aboratories should not simply use currently available disease-specific databases for directly filtering variants to determine which will be reported as disease causing. Few, if any, variant databases are curated to a clinical grade with strict, evidence-based consensus assessment of supporting data. It is well known that many databases contain misclassified variants, particularly benign variation misclassified as disease causing.”

    Joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, May 2015.

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Oncology

  • American College of Obstetrician and Gynecologists (ACOG)

    Genetic counseling and testing can be performed by an obstetrician-gynecologist or other gynecologic care provider who has expertise in cancer genetics.

    “[E]valuating a patient’s risk of hereditary breast and ovarian cancer syndrome should be a routine part of obstetric and gynecologic practice. […] Multigene panel testing may be useful when more than one gene may be associated with an inherited cancer syndrome.”

    Practice Bulletin from American College of Obstetrician and Gynecologists Committee and the Society of Gynecologic Oncology, August 2017.

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  • American Society of Breast Surgeons (ASBrS)

    Consensus Guideline on Genetic Testing for Hereditary Breast Cancer

    “Genetic testing should be made available to all patients with a personal history of breast cancer.”

    The American Society of Breast Surgeons. Consensus Guideline on Genetic Testing for Hereditary Breast Cancer. February 10, 2019.

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  • American Society of Clinical Oncology (ASCO)

    ASCO recommends all women with epithelial ovarian cancer should be offered a germline testing of an ovarian cancer panel that includes a minimum of these 10 genes: BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, MLH1, MSH2, MSH6, PMS2, and PALB2

    “All women diagnosed with epithelial ovarian cancer should be offered germline genetic testing for BRCA1, BRCA2, and other ovarian cancer susceptibility genes, irrespective of their clinical features or family cancer history.”

    Konstantinopoulos PA, et al. Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer: ASCO Guideline J. Clin. Oncol. 2020 Apr 10; 38(11):1222-1245.

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    ASCO guidelines on Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer.

    “Many women with node-negative breast cancer should consider extended therapy for up to a total of 10 years of adjuvant endocrine treatment based on considerations of recurrence risk using established prognostic factors [stage, grade, and genomic signatures].”

    Burstein HJ, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: ASCO Clinical Practice Guideine Focused Update. J Clin Oncol. 2018 Nov 19. Epub ahead of print

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    ASCO guidelines on adjuvant systemic therapy for women with early-stage invasive breast cancer.

    “[T]he panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer.”

    Harris LN, Ismaila N, McShane LM, et al. American Society of Clinical Oncology. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016 Apr 1; 34(10):1134-50.

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    Several studies demonstrate the prevalence of mutations identified by panel-based testing.

    “The use of germline multiplex or multigene panel testing is rapidly expanding in cancer risk assessment. Potential advantages to such testing include time and cost efficiency, decrease in testing fatigue for patients and providers, efficient use of a single specimen, and comprehensive assessment for cancer susceptibility, particularly in common cancers or individuals without identifiable syndromes. This type of testing may be particularly useful in situations where there are multiple high-penetrance genes associated with a specific cancer, the prevalence of actionable mutations in one of several genes is high, and it is difficult to predict which gene may be mutated on the basis of phenotype or family history.”

    Robson ME, et al. American Society of Clinical Oncology policy statement update: Genetic and genomic testing for cancer susceptibility. J Clin Oncol 2015 Nov; 33(31):3660-67.

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  • National Society of Genetic Counselors (NSGC)

    NSGC endorses multi-gene panel tests.

    “The National Society of Genetic Counselors (NSGC) endorses the use of multi-gene panel tests when clinically warranted and appropriately applied. These tests can provide a comprehensive and efficient route to identifying the genetic causes of disease. Before ordering a multi-gene panel test, providers should thoroughly evaluate the analytic and clinical validity of the test, as well as its clinical utility. Additional factors to consider include, but are not limited to: clinical and family history information, gene content of the panel, limitations of the sequencing and informatics technologies, and variant interpretation and reporting practices.”

    National Society of Genetic Counselors (NSGC), March 2017.

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  • National Institute of Health and Care Excellence (NICE)

    National Institute of Health and Care Excellence (NICE) – Guidance for patients with early breast cancer.

    “EndoPredict (Epclin score), Oncotype DX® Breast Recurrence Score and Prosigna® are recommended as options for guiding adjuvant chemotherapy decisions for people with [ER-positive, HER2-negative], and lymph node-negative early breast cancer.”

    NICE Guidance – December 19, 2018

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  • Society of Gynecologic Oncology (SGO)

    Genetic predisposition for particular cancers is changing from individual genes and syndromes to multiplex testing for a number of genes.

    “Evaluation of the likelihood of a patient having [one of the] gynecologic cancer predisposition syndromes enables physicians to provide individualized assessments of cancer risk, as well as the opportunity to provide tailored screening and prevention strategies such as surveillance, chemoprevention, and prophylactic surgery that may reduce the morbidity and mortality associated with these syndromes.”

    Lancaster JM, et al. Society of Gynecologic Oncology statement on risk assessment for inherited gynecologic cancer predispositions. Gynecologic Oncology 2015; 136:3–7.

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Urology

  • American Association of Clinical Urologists (AACU)

    Prolaris promotes accurate selection of men for active surveillance.

    “There is an urgency to incorporating newly available laboratory tools into the evaluation and management of prostate cancer to promote the accurate selection of men for active surveillance and to identify those who may be better served with multimodal treatment rather than monotherapy. Better patient selection for active surveillance will reduce the burden of over-treatment of indolent disease. Further, it is incumbent on urologists to obtain detailed family cancer histories and to consider hereditary genetic testing when family history patterns suggest risk.”

    American Association of Clinical Urologists (AACU) and the Large Urology Group Practice Association (LUGPA). Position statement: Genomic testing in prostate cancer. February 2018.

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  • Washington State Health Care Authority

    Gene expression profile (GEP) testing is a covered benefit when test results will impact treatment decisions.

    “Prostate cancer tests Oncotype DX and Prolaris are covered only for low risk or favorable intermediate risk disease.”

    Washington State Health Care Authority. Health Technology Clinical Committee Findings and Decision: Gene expression profile testing of cancer tissue, May 2018.

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Women’s Health

  • American College of Medical Genetics and Genomics (ACMG)

    Carrier Screening

    ACMG Policy Statement: ACMG position statement on prenatal/preconception expanded carrier screening.

    “The organization has defined the standard of care for prenatal/preconception population carrier screening for common single-gene autosomal recessive disorders (such as cystic fibrosis and spinal muscular atrophy) and a panel of single-gene autosomal recessive conditions specifically for the Ashkenazi Jewish population.”

    Grody, W., Thompson, B., Gregg, A. et al. ACMG position statement on prenatal/preconception expanded carrier screening.  Genet Med 15, 482–483 (2013). https://doi.org/10.1038/gim.2013.47.

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    Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine.

    “ACMG, ACOG, NSGC, PQF, and SMFM state that carrier screening for inherited genetic conditions is an important component of preconception and prenatal care.”

    Edwards, J. G., et al. Expanded Carrier Screening in Reproductive Medicine—Points to Consider.  Obstetrics & Gynecology, 2015;125(3), 653–662.

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    Prenatal Screening

    ACMG Position Statement: Noninvasive prenatal screening for fetal aneuploidy.

    “New evidence strongly suggests that NIPS can replace conventional screening for Patau, Edwards, and Down syndromes across the maternal age spectrum.”

    Gregg AR, Bajaj K, Benkendorf JL, Best RG, Monaghan KG, Skotko BG, et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016;18:1056-65. PMID: 27467454.

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  • American College of Obstetrician and Gynecologists (ACOG)

    Carrier Screening

    ACOG Committee Opinion No. 690: Carrier Screening in the Age of Genomic Medicine.

    “ACOG recommends that all patients considering pregnancy or already pregnant be offered carrier screening for cystic fibrosis and spinal muscular atrophy. Expanded carrier screening is an acceptable screening strategy for prepregnancy and prenatal carrier screening.”

    Carrier screening in the age of genomic medicine. Committee Opinion No. 690. American College of Obstetricians and Gynecologists. Obstet Gynecol 2017; 129:e35-40.

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    ACOG Committee Opinion No. 691: Carrier Screening for Genetic Conditions.

    “ACOG recommends information about genetic carrier screening be provided to every pregnant woman.”

    Carrier screening for genetic conditions. Committee Opinion No. 691. American College of Obstetricians and Gynecologists. Obstet Gynecol 2017;129:e41-55.

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    Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine.

    “ACMG, ACOG, NSGC, PQF, and SMFM state that carrier screening for inherited genetic conditions is an important component of preconception and prenatal care.”

    Edwards, J. G., et al. Expanded Carrier Screening in Reproductive Medicine—Points to Consider.  Obstetrics & Gynecology, 2015;125(3), 653–662.

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    Prenatal Screening

    ACOG & SMFM Practice Bulletin No. 163: Screening for Fetal Aneuploidy.

    “ACOG and SMFM recognize cell-free DNA testing as a screen for aneuploidy.”

    Rose NC and Mercer BM. Practice Bulletin No. 163 Summary: Screening for Fetal Aneuploidy. Obstet Gynecol. 2016;127:979–81. PMID: 27101120.

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  • International Society for Prenatal Diagnosis (ISPD)

    Prenatal Screening

    ISPD Position Statement from the Chromosome Abnormality Screening Committee.

    “cfDNA screening as a primary tests offered to all pregnant women is currently considered appropriate by ISPD.”

    Benn P, Borrell A, Chiu RW, Cuckle H, Dugoff H, Fass B, et al. Position statement from the Chromosome Abnormality Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis. Prenat Diagn. 2015;35:725-34. PMID: 25970088

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  • National Society of Genetic Counselors (NSGC)

    Carrier Screening

    Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine.

    “ACMG, ACOG, NSGC, PQF, and SMFM state that carrier screening for inherited genetic conditions is an important component of preconception and prenatal care.”

    Edwards, J. G., et al. Expanded Carrier Screening in Reproductive Medicine—Points to Consider.  Obstetrics & Gynecology, 2015;125(3), 653–662.

    View Article

    Prenatal Screening

    NSGC Position Statement: Prenatal Cell-Free DNA Screening.

    “The National Society of Genetic Counselors supports prenatal cell-free DNA screening, also known as NIPT or NIPS, as an option for pregnant patients.”

    National Society of Genetic Counselors. Position Statements: “Prenatal Cell-Free DNA Screening.” 2016. https://www.nsgc.org/p/bl/et/blogaid=805 (accessed 3/2/2018).

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  • Perinatal Quality Foundation (PQF)

    Carrier Screening

    Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine.

    “ACMG, ACOG, NSGC, PQF, and SMFM state that carrier screening for inherited genetic conditions is an important component of preconception and prenatal care.”

    Edwards, J. G., et al. Expanded Carrier Screening in Reproductive Medicine—Points to Consider.  Obstetrics & Gynecology, 2015;125(3), 653–662.

    View Article

  • Society for Maternal-Fetal Medicine (SMFM)

    Carrier Screening

    Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine.

    “ACMG, ACOG, NSGC, PQF, and SMFM state that carrier screening for inherited genetic conditions is an important component of preconception and prenatal care.”

    Edwards, J. G., et al. Expanded Carrier Screening in Reproductive Medicine—Points to Consider.  Obstetrics & Gynecology, 2015;125(3), 653–662.

    View Article

    Prenatal Screening

    ACOG & SMFM Practice Bulletin No. 163: Screening for Fetal Aneuploidy.

    “ACOG and SMFM recognize cell-free DNA testing as a screen for aneuploidy.”

    Rose NC and Mercer BM. Practice Bulletin No. 163 Summary: Screening for Fetal Aneuploidy. Obstet Gynecol. 2016;127:979–81. PMID: 27101120.

    View Statement

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