lunes, 3 de diciembre de 2012

Genomics|Genetic Testing|Tier 1-3

Genomics|Genetic Testing|Tier 1-3

Genetic Testing

Genomic Tests and Family History by Levels of Evidence

The CDC Office of Public Health Genomics provides the following list of genomic tests and applications in practice according to three levels of evidence based on the paper by Khoury et alExternal Web Site Icon. This list is provided only for informational purposes to researchers, providers, public health programs and others. The most recent additions to the list are applications relevant to family health history based on existing recommendations from the US Preventive Services Task Force. For additional information on updates to this list, read our accompanying blog.
Tier 1 genomic and family health history applications are recommended for clinical use by evidence-based panels based on a systematic review of analytic validity, clinical validity and utility for specific clinical scenarios


Test/ApplicationScenarioEvidence-based recommendation
Newborn screening panel of 31 core conditionsScreening all newborns at birth through public health programsSecretary's Advisory Committee on Heritable Diseases of Newborns and ChildrenExternal Web Site Icon (2011)
BRCA genetic counseling/ BRCA genetic testingReferral to genetic counseling of women with specific family history patterns of breast or ovarian cancerUS Preventive Services Task ForceExternal Web Site Icon (2005) [Update in progressExternal Web Site Icon]
Additional Information:
NCCN Guideline: Genetic/Familial High-Risk Assessment: Breast and Ovarian Cancer Adobe PDF file [PDF 615.35 KB]External Web Site Icon (2012)
Lynch syndrome testingScreening newly diagnosed cases of colorectal cancer for Lynch syndrome and cascade testing of relatives of affected Lynch syndrome casesRecommendations of the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives (2009)
Additional Information:
NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in OncologyExternal Web Site Icon (2011)
Familial HypercholesterolemiaCascade cholesterol testing with/without DNA analysis among relatives of affected persons with familial hypercholesterolemiaNICE Guideline: Identification and management of familial hypercholesterolaemia Adobe PDF file [PDF 746.30 KB]External Web Site Icon (2008)
HLA testing for abacavir sensitivityTesting HIV patients before starting abacavir to reduce adverse effects and inform drug choiceDHHS Advisory Committee on HIV treatment: Guidelines for the Use of Antiretroviral Agents in HIV-1-infected Adults and Adolescents Adobe PDF file [PDF 3.01 MB]External Web Site Icon (2012)
HER2 mutation testing in breast cancerRoutine testing for HER2 mutations in patients with invasive breast cancer to target therapyNICE Guideline: Early and locally advanced breast cancer: diagnosis and treatment. Adobe PDF file [PDF 2 MB]External Web Site Icon (2009)
Additional Information:
American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancerExternal Web Site Icon. (2007)
EGFR mutation tumor analysis in Non-small Cell Lung Cancer

Predictive for therapyNICE Guideline: Erlotinib for the first-line treatment of locally advanced or metastatic EGFR-TK mutation-positive non-small cell lung cancer. Adobe PDF file [PDF 189.11 KB]External Web Site Icon (2012)
Additional information:
NCCN Clinical Practice Guidelines in Oncology: Non–Small Cell Lung Cancer. Version 3. Adobe PDF file [PDF 1.31 MB] External Web Site Icon (2012) [by free subscription only]
BCBSA Tec Evaluation - Epidermal Growth Factor Receptor Mutations and Tyrosine Kinase Inhibitor Therapy in Advanced Non-Small-Cell Lung Cancer. Adobe PDF file [PDF 195.47 KB]External Web Site Icon (2011)
First-degree family history of breast cancerTo inform discussion of chemoprevention for breast cancer for women; consider with age and other risk factors to identify high risk for breast cancer and low risk for adverse effects US Preventive Services Task Force: Chemoprevention of Breast CancerExternal Web Site Icon (2002)
Family history of cardiovascular disease before age 50 years in male relatives and age 60 years in female relatives To inform earlier start to screening for cholesterol abnormalities for men and women (starting at age 20 years); use to identify increased risk for lipid disorders US Preventive Services Task Force: Screening for Lipid Disorders in AdultsExternal Web Site Icon (2008)
Parental history of fractureTo inform (in combination with other risk factors) earlier start to screening for osteoporosis in women US Preventive Services Task Force: Screening for OsteoporosisExternal Web Site Icon (2011)
Family history, especially siblings, with hereditary hemochromatosisCounseling for genetic testing for hereditary hemochromatosis among asymptomatic peopleUS Preventive Services Task Force: Screening for HemochromatosisExternal Web Site Icon (2006)
Family history of breast or ovarian cancer that includes a relative with a known deleterious BRCA mutationReferral to counseling for BRCA genetic testing for womenUS Preventive Services Task Force: Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer SusceptibilityExternal Web Site Icon (2005)

Tier 2 genomic and family health history applications have demonstrated analytic and clinical validity; hold promise for clinical utility but evidence-based panels have not examined their use or found insufficient evidence for their use. Such applications may provide information for informed decision making by providers and patients


Test/ApplicationScenarioEvidence-based recommendation
Breast cancer gene expression profilesTo estimate risk of recurrence of breast cancer and target therapyRecommendations from the EGAPP Working Group: Can tumor gene expression profiling improve outcomes in patients with breast cancer?External Web Site Icon (2009)
NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology.External Web Site Icon (2011)
Oncotype Dx in ER+/node negative patientsPrognostic risk recurrence and selection of treatmentNCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology.External Web Site Icon (2011)
ER-alpha/PgR (ESR1/PR) tumor protein analysis in Breast Cancer patientsTo estimate the prognostic and predictive response to ER-alpha (ESR1)-modulating agentsNCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology.External Web Site Icon (2011)

NCCN Task Force Report: Estrogen receptor and progesterone receptor testing in breast cancer immunohistochemistry.
External Web Site Icon
(2009)
American Society of Clinical Oncology/College of American Pathologist guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer.External Web Site Icon (2010)
Kras mutations [except c38G>A) NSCLC and CRC tumor analysisPredictive (negative for anti-EGFR therapy); negatively prognostic in several first-line randomized studiesNCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in OncologyExternal Web Site Icon. (2011)

BCBSA TEC: KRAS Mutations and Epidermal Growth Factor Receptor Inhibitor Therapy in Metastatic Colorectal Cancer. (2009, BCBSA personal communication)
CEACAM5 (CEA) serum analysis in colon cancerBaseline monitoring/regular testing for surveillance for Colon Cancer NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in OncologyExternal Web Site Icon. (2011)

NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. Version 3 Adobe PDF file [PDF 1.06 MB]External Web Site Icon (2012) [by free subscription only]
ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer.External Web Site Icon (2006)
BRAF c.1799T>A (p.V600E) mutation tumor analysis in colon cancerPrognostic (negative prognostic marker); Predictive (negative for anti-EGFR therapy) in colon cancer patientsNCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in OncologyExternal Web Site Icon. (2011)

NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. Version 3. Adobe PDF file [PDF 1.06 MB]External Web Site Icon (2012) [by free subscription only]
ALK gene fusion tumor analysisPredictive for crizotinib therapyNCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in OncologyExternal Web Site Icon. (2011)
NCCN Clinical Practice Guidelines in Oncology: Non–Small Cell Lung Cancer. Version 2. Adobe PDF fileExternal Web Site Icon (2012) [by free subscription only]
FLT3-ITD tumor analysis for Acute Myeloid LeukemiaPredictive/prognostic FLT3-ITD confers poor risk statusNCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in OncologyExternal Web Site Icon. (2011)

NCCN Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia. Version 2. Adobe PDF file [PDF 790.06 KB]External Web Site Icon (2011) [by free subscription only]
CEBPA mutation tumor analysis for Acute Myeloid LeukemiaPredictive/prognostic may confer better risk statusNCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in OncologyExternal Web Site Icon. (2011)
NPM1 mutation tumor analysis for Acute Myeloid LeukemiaPredictive/prognostic may confer better risk statusNCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in OncologyExternal Web Site Icon. (2011)
KIT mutation tumor analysis for Acute Myeloid LeukemiaPredictive/prognostic may confer higher risk of relapseNCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in OncologyExternal Web Site Icon. (2011)
First-degree family history of abdominal aortic aneurysm requiring surgical repair Consider for identifying men and women for one-time screening for abdominal aortic aneurysmUS Preventive Services Task Force: Screening for Abdominal Aortic AneurysmExternal Web Site Icon (2005)
First-degree family history of colorectal cancer at a younger age or multiple affected first-degree relativesConsider to inform earlier start to colorectal cancer screening for men and women;US Preventive Services Task Force: Screening for Colorectal CancerExternal Web Site Icon (2008)
Parental history of depressionConsider with other risk factors when screening adolescents for major depressive disorderUS Preventive Services Task Force: Major Depressive Disorder in Children and AdolescentsExternal Web Site Icon (2009)
Family history of depressionConsider with other risk factors when screening adults for depressionUS Preventive Services Task Force: Screening for Depression in AdultsExternal Web Site Icon (2009)
Family history of bladder cancerConsider with other risk factors when determining whether to screen adults for bladder cancerUS Preventive Services Task Force: Screening for Bladder Cancer in AdultsExternal Web Site Icon (2011)
Family history of developmental dysplasia of the hip (DDH)Consider with other risk factors when determining whether to screen infants for DDHUS Preventive Services Task Force: Screening for Developmental Dysplasia of the HipExternal Web Site Icon (2006)
Family history of diabetesConsider with other risk factors when determining whether to screen for gestational diabetes mellitusUS Preventive Services Task Force: Screening for Gestational Diabetes MellitusExternal Web Site Icon (2008)
Family history of neonatal jaundiceConsider with other risk factors when determining whether to screen infants for hyberbilirubinemiaUS Preventive Services Task Force: Screening Infants for Hyperbilirubinemia to Prevent Chronic Bilirubin EncephalopathyExternal Web Site Icon (2009)
Family history of age-related macular degenerationConsider with other risk factors when determining whether to screen older adults for visual acuityUS Preventive Services Task Force: Screening for Impaired Visual Acuity in Older AdultsExternal Web Site Icon (2009)
Family history relevant to dyslipidemia (otherwise undefined)Consider with other risk factors when determining whether to screen infants, children, adolescents, or young adults (up to age 20 for lipid disordersUS Preventive Services Task Force: Screening for Lipid Disorders in ChildrenExternal Web Site Icon (2007)
Additional Information:
Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Summary ReportExternal Web Site Icon
Family history of skin cancerConsider with other risk factors when determining whether to screen adults for skin cancerUS Preventive Services Task Force: Screening for Skin CancerExternal Web Site Icon (2009)
Family history of chronic kidney diseaseConsider with other risk factors when determining whether to screen adults for chronic kidney diseaseUS Preventive Services Task Force: Screening for Chronic Kidney DiseaseExternal Web Site Icon (2012)
Family history for common diseasesCollecting family history in primary care for risk assessment of common diseasesNIH state-of science panel found insufficient evidenceExternal Web Site Icon (2009)
Pharmacogenomic testingUse of pharmacogenomics tests to inform safety and effectiveness of existing medicationsPharmacogenomics information on labels of more than 113 FDA approved drugsExternal Web Site Icon; The Clinical Pharmacogenetics Implementation ConsortiumExternal Web Site Icon issues guidelines to help clinicians understand how available genetic test results should be used to optimize drug therapy, rather than whether tests should be ordered.
Single gene disorders and chromosomal abnormalitiesMolecular, cytogenetic biochemical and other tests available for the diagnosis, management and carrier testing for these disordersMore than 2500 geneticExternal Web Site Icon conditions affect millions of individuals. Diagnosis and management of these conditions may require use of genetic tests even without formal evidence synthesis and reviews by evidence panels. The NIH Genetic Testing RegistryExternal Web Site Icon has updated information on genetic tests in practice.


Tier 3 genomic and family health history applications have not demonstrated adequate analytic validity, clinical validity, or clinical utility. This also includes applications for which evidence-based panels have recommended against their use based on the synthesis of the balance of benefits and harms. Such applications are not ready for routine practice, but may be considered in clinical and population research.


Test/ApplicationScenarioEvidence-based recommendation
Hereditary hemochromatosisRoutine genetic screening for hereditary hemochromatosis in the asymptomatic population.US Preventive Services Task Force: Screening for HemochromatosisExternal Web Site Icon (2006)
BRCA genetic counseling, BRCA testingRoutine referral for genetic counseling or routine BRCA testing for women whose family history is not associated with an increased risk of BRCA mutationsUS Preventive Services Task Force: Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer SusceptibilityExternal Web Site Icon (2005)
Genetic risk factors for common diseasesRisk assessment and disease preventionMultiple panels have recommended against use of genetic risk factors testing. EGAPP made specific recommendations against testing for factor V LeidenExternal Web Site Icon and cardiogenomic profilesExternal Web Site Icon
Emerging genomic tests found in the CDC's GAPP FinderExternal Web Site Icon of the GAPP Knowledge BaseExternal Web Site IconMore than 400 genomic tests for various intended uses captured through horizon scanningAlmost all of these applications (except when listed above) have insufficient information on analytic or clinical validity, or clinical utility
Next Generation Sequencing/ Whole Genome SequenceEmerging tools to help with diagnosis of rare familial diseases and provide information for assessing risk for common diseasesRapidly evolving landscape; gaps in knowledge exist for analytic validity, clinical validity and clinical utility

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