Comprender su resultado positivo Guía para comprender sus riesgos y tomar medidas

1

PRIMERA PARTE:

Comprender su resultado El resultado de su prueba podría incluir tres partes: el Resultado de la prueba genética, su riskScore™ para cáncer de mama (si corresponde) y el Análisis de su historia clínica.

Resultado de la prueba genética A. El resumen de los resultados de su prueba Myriad myRisk® Hereditary Cancer se incluye en la primera página del informe. 1. E  l resultado de su prueba myRisk Genetic Result es POSITIVO. Esto significa que obtuvo un resultado positivo en el estudio de una mutación de uno o más genes. Uno o más de uno de los genes que se trasmiten en su familia presenta una variación o es portador de una mutación genética que aumenta su riesgo de presentar un tipo o más de un tipo de cáncer hereditario. Esta(s) mutación(es) es de RELEVANCIA CLÍNICA y podría ser conveniente realizar cambios en su manejo médico. 2. Su resultado podría incluir un riskScore™ para cáncer de mama. Si se realizó el riskScore, se incluirá información detallada en la página siguiente del Informe de resultado de su prueba genética (ver E.) 3. Su resultado incluirá un Análisis de historia clínica. Este análisis se basa en los factores de riesgo clínicos personales y los antecedentes familiares de cáncer que usted informó a su proveedor. Si el análisis identificó algún tipo de manejo médico modificado, aparecerá un asterisco naranja . Se incluirá un resumen de las recomendaciones para el manejo médico basadas en las principales pautas establecidas por la sociedad médica en la sección Herramienta de Manejo myRisk de su informe. B. Su informe le brinda información detallada sobre la mutación genética específica que se detectó y su mayor riesgo de presentar tipos de cáncer asociados. Con esta información, usted y su proveedor de atención médica podrán crear un plan de manejo médico adecuado para usted. C. Sumado a su resultado positivo, sus pruebas podrían haber detectado una o más de una “variante genética de importancia incierta". En la actualidad se desconoce si una variante genética de importancia incierta se asocia con un mayor riesgo de cáncer. Myriad ha asumido un compromiso vitalicio de trabajar para comprender

RE P ORT E X A M P LE Myriad myRisk® Hereditary Cancer Test

myRisk Genetic Result RE CE I VI N G H E A LT H CA RE PRO VI D E R

SPE CI M E N

Physician Name, MD Myriad Healthcare Partners 320 Wakara Way Salt Lake City, UT 84108

Specimen Type: Draw Date: Accession Date: Report Date:

PAT I E N T

Buccal Aug 15, 2017 Aug 30, 2017 Sept 4, 2017

O RD E RI N G PH YSI CI A N : Physician Name, MD

A

Name: Date of Birth: Patient ID: Gender: Accession #: Requisition #:

Case Study 4 Jan 1, 1980 0000 Female 00000000-000 000000

MYRISK GENETIC RESULT: POSITIVE clinically significant mutation identified

BREAST CANCER RISKSCORE™: REMAINING LIFETIME RISK 23.6% This level of risk is at or above 20% threshold for consideration of modified medical managament. See riskScore™ Interpretation Section for more information.

CLINICAL HISTORY ANALYSIS: NO MODIFIED MEDICAL MANAGEMENT GUIDELINES WERE IDENTIFIED BASED ON THE INFORMATION PROVIDED. Other clinical factors may influence individualized management. This analysis may be incomplete if details about cancer diagnoses, ages, family relationships or other factors were omitted or ambiguous.

B

GENE

MUTATION

INTERPRETATION

MLH1

c.133del (p.Thr45Glnfs*5) Heterozygous

HIGH CANCER RISK This patient has Lynch syndrome, Hereditary Non-Polyposis Colon Cancer (HNPCC).

DETAILS ABOUT: MLH1 c.133del (p.Thr45Glnfs*5): NM_000249.3; AKA: 133delA Functional Significance: Deleterious – Abnormal Protein Production and/or Function The heterozygous germline MLH1 mutation c.133del is predicted to result in the premature truncation of the MLH1 protein at amino acid position 49 (p.Thr45Glnfs*5). Clinical Significance: High Cancer Risk This mutation is associated with increased cancer risk and should be regarded as clinically significant.

C

ADDITIONAL FINDINGS: NO VARIANT(S) OF UNCERTAIN SIGNIFICANCE (VUS) IDENTIFIED Details About Non-Clinically Significant Variants: All individuals carry DNA changes (i.e., variants), and most variants do not increase an individual’s risk of cancer or other diseases. When identified, variants of uncertain significance (VUS) are reported. Likely benign variants (Favor Polymorphisms) and benign variants (Polymorphisms) are not reported and available data indicate that these variants most likely do not cause increased cancer risk. Present evidence does not suggest that non-clinically significant variant findings be used to modify patient medical management beyond what is indicated by the personal and family history and any other clinically significant findings. Variant Classification: Myriad’s myVision® Variant Classification Program performs ongoing evaluations of variant classifications. In certain cases, healthcare providers may be contacted for more clinical information or to arrange family testing to aid in variant classification. When new evidence about a variant is identified and determined to result in clinical significance and management change, that information will automatically be made available to the healthcare provider through an amended report.

© 2017 Myriad Genetics, Inc. | 320 Wakara Way, Salt Lake City, Utah 84108 | PH: 1-800-469-7423 FX: 801-584-3615 The format and contents of this report are proprietary and may not be copied or used without permission, except for purposes of diagnosing, counseling and treating the patient identified in the report and members of his or her family. Myriad, Myriad myRisk, riskScore, BRACAnalysis, COLARIS, myVision and their respective logos are either trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions.

myRisk Genetic Result: Page 1 of 3

Resultado positivo en la prueba de UNA MUTACIÓN ESPECÍFICA: Si un miembro de su familia obtiene un resultado positivo en el estudio de una mutación, es posible que su proveedor le haya indicado que se haga la prueba solamente para esa mutación, a fin de determinar si usted también la tiene. Esto se denomina prueba de una mutación específica. Si obtiene un resultado positivo en la prueba que estudia una mutación específica, usted EFECTIVAMENTE es portador de la mutación que está presente en su familia y debe conversar sobre los cambios necesarios en su manejo médico con su proveedor de atención médica. Debido a que las pruebas de mutaciones específicas no estudian otras mutaciones ni los antecedentes familiares, la información es limitada. Los resultados positivos en las pruebas de una mutación específica incluirán una Herramienta de Manejo myRisk que corresponde ÚNICAMENTE a su mutación genética.

la naturaleza de estas variantes. Si surgen nuevos datos sobre una variante, esa información se pondrá a disposición de su proveedor de atención médica quien se pondrá en contacto con usted para compartir la información actualizada. Es importante comprender que las intervenciones médicas no debe basarse en un resultado de variante genética de importancia incierta.

CONFI D E NT I A L

myRisk Genetic Result Name: Case Study 4

D. Puede consultar una lista de todos los genes examinados en la sección Genes analizados.

DOB: Jan 1, 1980

Accession #: 00000000-000

Report Date: Sept 4, 2017

ADDITIONAL INFORMATION

D

Indication for Testing: It is our understanding that this individual was identified for testing due to a personal or family history suggestive of a hereditary predisposition for cancer.

GENES ANALYZED Unless otherwise noted sequencing and large rearrangement analyses were performed on the following genes:

Associated Cancer Risks and Clinical Management: Please see the “myRisk Management Tool” associated with this report for a summary of cancer risk and professional society medical management guidelines that may be useful in developing a plan for this patient based on test results and reported personal/family history, if applicable. Testing of other family members may assist in the interpretation of this patient’s test result.

APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM (large rearrangement only), MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53. Sequencing was performed for select regions of POLE and POLD1. and large rearrangement analysis was performed for select regions of GREM1 (see technical specifications).

Analysis Description: The Technical Specifications summary (MyriadPro.com/myRisk) describes the analysis, method, performance, nomenclature, and interpretive criteria of this test. The classification and interpretation of all variants identified in this assay reflects the current state of scientific understanding at the time this report was issued, and may change as new scientific information becomes available. The interpretation of this test may be impacted if the patient has a hematologic malignancy or an allogeneic bone marrow transplant.

**Other genes not analyzed with this test may also be associated with cancer.

CLASSIFICATION DISCLAIMER THE CLASSIFICATION AND INTERPRETATION OF ALL VARIANTS IDENTIFIED IN THIS ASSAY REFLECTS THE CURRENT STATE OF MYRIAD’S SCIENTIFIC UNDERSTANDING AT THE TIME THIS REPORT WAS ISSUED. VARIANT CLASSIFICATION AND INTERPRETATION MAY CHANGE FOR A VARIETY OF REASONS, INCLUDING BUT NOT LIMITED TO, IMPROVEMENTS TO CLASSIFICATION TECHNIQUES, AVAILABILITY OF ADDITIONAL SCIENTIFIC INFORMATION, AND OBSERVATION OF A VARIANT IN MORE PATIENTS.

E. Si se realizó el riskScore™, esta página de su Informe de resultado de su prueba genética incluirá detalles del análisis. Esta página muestra una estimación de su riesgo de presentar cáncer de mama durante el resto de su vida así como su riesgo para los próximos cinco años. Puede comparar su riesgo con el de la población general usando el gráfico que se incluye. Si el análisis identificó algún tipo de manejo médico modificado sobre la base de su riskScore, aparecerá un asterisco naranja al lado de su puntaje. Se incluirá un resumen de las recomendaciones para el manejo médico basadas en las principales pautas establecidas por la sociedad médica en la sección Herramienta de Manejo myRisk de su informe.

CONFI D E NT I A L

myRisk Genetic Result Name: Case Study 4

DOB: Jan 1, 1980

Accession #: 00000000-000

Report Date: Sept 4, 2017

Breast Cancer riskScore™

E Breast Cancer riskScore™

RESULT: 23.6% Remaining Lifetime Risk for Breast Cancer 0.8% 5-Year Risk for Breast Cancer

23.6%

Breast Cancer riskScore™ - Remaining Lifetime Risk 20% Risk © 2017 Myriad Genetics, Inc. | 320 Wakara Way, Salt Lake City, Utah 84108 | PH: 1-800-469-7423 FX: 801-584-3615 Threshold The format and contents of this report are proprietary and may not be copied or used without permission, except for purposes of diagnosing, counseling and treating the patient identified in the report and members of his or her family. Myriad, Myriad myRisk, riskScore, BRACAnalysis, COLARIS, myVision and their respective logos are either trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions.

13.1%

General Population

myRisk Genetic Result: Page 2 of 3

23.6%

This Patient 0

5 Average Risk

10

15

20

25

30

35

40

45

>50

Above Average Risk

BREAST CANCER RISKSCORE ™ INTERPRETATION The breast cancer riskScore™ provides an estimate of the remaining lifetime risk for breast cancer. A risk estimate greater than 20% is associated with specific modified medical recommendations, including consideration of more aggressive breast cancer screening and additional risk reduction measures. If applicable, details of these recommendations are provided in the accompanying myRisk Medical Management Tool or other supplemental material. Women with a risk estimate below 20% may still be appropriate for consideration of modified medical management based on other clinical factors or estimates from other breast cancer risk models, such as Tyrer-Cuzick, Claus, and Gail. BREAST CANCER RISKSCORE ™ ANALYSIS DESCRIPTION The breast cancer riskScore™ provides 5-year and remaining lifetime breast cancer risks, based on an analysis of genetic markers combined with patient clinical and family history data. The Technical Specifications summary (https://www.myriadpro.com/documentsand-forms/technical-specifications/) describes the analysis, method, performance and interpretive criteria of this test. In some cases, due to biological or technical limitations, analyses of all ___ biomarkers may not be performed. It is unlikely that data from the un-analyzed markers would have a large impact on breast cancer risk estimates provided. ___/86 markers were analyzed for this patient. Clinical and CONFI DENTI AL family history data used for this analysis is shown in the Clinical and Cancer Family History Information section of this report. The accuracy of this information can significantly affect the provided breast cancer Family risk estimates. Clinical & Cancer History Information Name: Case Study 4

DOB: Jan 1, 1980

Accession #: 00000000-000

Report Date: Sept 4, 2017

Please contact Myriad Medical Services at 1-800-469-7423 X 3850 to discuss any questions regarding this result.

F. En la Página de información clínica e información sobre antecedentes familiares de cáncer se muestra la información sobre su historia clínica y los antecedentes personales y familiares de cáncer que informó.

This Authorized Signature pertains to this laboratory report:

These test results should only be used in conjunction with the patient’s clinical PATIENT CLINICAL HISTORY SUMMARY history and any previous analysis of appropriate family members. The patient’s clinical history and37 test results should Hormone not be disclosed to aTherapy third party, Replacement (HRT) unlessNo related to treatment or payment for treatment, without the patient’s express White/Non-hispanic - HRT: Treatment type N/A written authorization. It is strongly recommended that these results be Height 5”patient in a setting- HRT: user communicated to 5’ the that Current includes appropriate counseling.No This test was developed characteristics by N/A Weight 135 lbs. and its performance - Number of years agodetermined started Richard J. Wenstrup, MD Myriad Genetic Laboratories. It has not been cleared or approved by the U.S. Age of menarche 12 - Additional years of intended use N/A Diplomate ABMG Food and Drug Administration (FDA). The FDA has determined that clearance or Chief Medical Officer approval for laboratory-developed not Past required. Patient’s menopausal status Pre-menopausal tests is - HRT: user No

Benjamin B.Woman’s Roa, PhD age Diplomate ABMG Ancestry Laboratory Director

- Age of onset

N/A

- Number of years ago ended

Age of first live birth 24 Breast biopsy © 2017 Myriad Genetics, Inc. | 320 Wakara Way, Salt Lake City, Utah 84108 | PH: 1-800-469-7423 FX: 801-584-3615 The format and contents of this report are proprietary and may not be copied or used without permission, except for PERSONAL / FAMILY CANCER HISTORY SUMMARY* purposes of diagnosing, counseling and treating the patient identified in the report and members of his or her family. Myriad, Myriad myRisk, riskScore, BRACAnalysis, COLARIS, myVision and their respective logos are either trademarks or registered trademarks of Myriad Genetics, Inc. in the United States FA M ILY Mand E Mother B E R jurisdictions. C A N C E R / C L IN IC A L D IA G N O S IS

N/A No

myRisk A Genetic 3 of 3 G E AT DResult: I A G N O SPage IS

Patient

None

Mother

Colon

52

Maternal Aunt

Ovarian

45

--

N U M B E R O F PAT IE N T ’ S F E M A L E R E L AT IV E S Daughters: 0

Sisters: 2

Maternal Aunts: 2

Paternal Aunts: 1

The clinical information displayed here was provided by a qualified healthcare provider on the Test Request Form and other documents, and was not verified by Myriad. Family members listed as “other” are not included in a Tyrer-Cuzick breast cancer risk estimate or other personal/family history assessments. For more information see the Specifications for Personal/Family History Analysis at https://new.myriadpro.com/documents-and-forms/technical-specifications/.

F

© 2017 Myriad Genetics, Inc. | 320 Wakara Way, Salt Lake City, Utah 84108 | PH: 1-800-469-7423 FX: 801-584-3615 The format and contents of this report are proprietary and may not be copied or used without permission, except for purposes of diagnosing, counseling and treating the patient identified in the report and members of his or her family. Myriad, Myriad myRisk, riskScore, BRACAnalysis, COLARIS, myVision and their respective logos are either trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions.

Clinical & Family History Information: Page 1 of 1

Si tiene preguntas adicionales sobre su resultado, comuníquese con su proveedor de atención médica. El equipo de Servicios Médicos de Myriad también está disponible para ayudarlo: (800) 469-7423 x3850 / [email protected]

2

SEGUNDA PARTE:

Comprender sus riesgos Su riesgo de presentar cáncer en el futuro está determinado por el Resultado de su prueba genética, su historia clínica personal y sus antecedentes familiares de cáncer. La Herramienta de Manejo myRisk ofrece un resumen de sus riesgos basado en el resultado de su prueba genética y la información que suministró a Myriad. Sin embargo, debe conversar sobre los posibles factores de riesgo adicionales con su proveedor.

Herramienta de Manejo myRisk G. Tipos de cáncer asociados con su resultado positivo en la prueba myRisk Genetic Result. La parte superior de este informe indica que el resultado de su prueba genética es: POSITIVO. Puede consultar los riesgos de cáncer relacionados con su prueba myRisk Genetic Result en una tabla de riesgos de cáncer específicos asociados a su mutación genética. Esta tabla podría incluir intervalos de riesgo para estos tipos de cáncer en comparación con la población general (ver J.)

C ONF IDENTIAL

Myriad myRisk® Hereditary Cancer Test

myRisk Management Tool RECEIVING HEALTHCARE PROVIDER

SPECIM EN

Physician Name, MD Myriad Healthcare Partners 320 Wakara Way Salt Lake City, UT 84108

Specimen Type: Draw Date: Accession Date: Report Date:

PATIENT

Buccal Aug 15, 2017 Aug 30, 2017 Sept 4, 2017

Name: Date of Birth: Patient ID: Gender: Accession #: Requisition #:

ORDERING PHYSICIAN: Physician Name, MD

Case Study 4 Jan 1, 1980 0000 Female 00000000-000 000000

GENETIC TEST RESULTS SUMMARY INFORMATION MYRISK GENETIC RESULT: POSITIVE clinically significant mutation identified

BREAST CANCER RISKSCORE™: REMAINING LIFETIME RISK 23.6%

Los tipos de cáncer en esta tabla podrían figurar en rojo o naranja. El color rojo indica que el aumento del riesgo es significativamente superior al de la población general. El color naranja indica que el riesgo es elevado y es posible que no se conozca un porcentaje exacto en este momento. H. Podría recibir un riskScore™. El riskScore solo se calcula para las mujeres que tienen menos de 85 años, son de ascendencia europea únicamente y no tienen antecedentes personales de cáncer de mama, carcinoma lobular in situ (LCIS), hiperplasia, hiperplasia atípica o una biopsia de mama con resultados desconocidos. Este puntaje se calcula usando tanto factores genéticos como no genéticos que pueden ser comunes dentro de su familia. Es importante señalar que si su mutación genética conlleva un riesgo aumentado de cáncer de mama, su riesgo de cáncer de mama se definirá solo por el resultado de su prueba myRisk Genetic Result. Sin embargo, en caso de que se desconozca si su mutación genética conlleva un riesgo de cáncer de mama, su proveedor podría usar riskScore para comprender su riesgo de cáncer de mama. Si se calcula que su riskScore es del 20% o más, se incluirá un resumen de recomendaciones de manejo médico más adelante en el informe. I. Si es mujer, nunca recibió un diagnóstico de cáncer de mama y ninguno de sus familiares tiene una mutación genética conocida recibirá un Cálculo de riesgo con Tyrer-Cuzick. Tyrer-Cuzick es un modelo elaborado por reconocidos investigadores para predecir el riesgo que tiene una mujer de presentar cáncer de mama. El modelo de Tyrer-Cuzick considera tanto sus antecedentes familiares de cáncer como otros factores de riesgo clínicos personales. Si su Cálculo de riesgo con Tyrer-Cuzick es del 20% o más, se incluirá un resumen de recomendaciones de manejo médico más adelante en el informe.

This level of risk is at or above 20% threshold for consideration of modified medical managament. See riskScore™ Interpretation Section for more information.

CLINICAL HISTORY ANALYSIS: NO MODIFIED MEDICAL MANAGEMENT GUIDELINES WERE IDENTIFIED BASED ON THE INFORMATION PROVIDED. Other clinical factors may influence individualized management. This analysis may be incomplete if details about cancer diagnoses, ages, family relationships or other factors were omitted or ambiguous.

GENE

MLH1

H

THIS GENETIC TES T RESULT IS AS S OC IATED WITH THE FOLLOWING C ANC ER R IS K S :

M UTATION c.133del (p.Thr45Glnfs*5)

ELEVATED RISK: Pancreatic THIS R IS K S C OR E ™ RESULT IS AS S OC IATED WITH THE FOLLOWING C ANC ER R IS K S :

BR EAST CANC ER R IS K S C OR E ™

ELEVATED RISK: Breast

at or above 20%

I

G

HIGH RISK: Gastric, Colorectal, Endometrial, Ovarian

ADDITIONAL FINDINGS: NO VARIANT(S) OF UNCERTAIN SIGNIFICANCE (VUS) IDENTIFIED TYRER-CUZICK BREAST CANCER RISK CALCULATION LIFETIME BREAST CANCER RISK: 11.5%

5-YEAR BREAST CANCER RISK: 0.4%

The Tyrer-Cuzick breast cancer risk estimate is not calculated if one or more of the following conditions apply: the woman is known to carry a mutation in a gene associated with breast cancer risk, age is 85 or older, or if the sample was submitted with a version of the Test Request Form that does not include all of the fields required to collect the clinical information used in the calculation. Version 7.02 of the Tyrer-Cuzick model was used for this risk estimate. Tyrer-Cuzick model Versions 7.02 and 8.0 are available for download at the EMS-Trials website, http://www.ems-trials.org/riskevaluator.

CONFI DENTI AL © 2017 Myriad Genetics, Inc. | 320 Wakara Way, Salt Lake City, Utah 84108 | PH: 1-800-469-7423 FX: 801-584-3615 The format and contents of this report are proprietary and may not be copied or used without permission, except for purposes of diagnosing, counseling and treating the patient identified in the report and members of his or her family. Myriad, Myriad myRisk, riskScore, BRACAnalysis, COLARIS, myVision and their respective logos are either trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions.

myRisk Medical Management Name: Case Study 4

ManagementReport Tool: Page of 74, 2017 Accession #: myRisk 00000000-000 Date: 1Sept

DOB: Jan 1, 1980

WHAT ARE THE PATIENT’S GENE-RELATED CANCER RISKS? If more than one gene mutation increases a specific cancer risk (e.g., breast), only the highest cancer risk is shown. If this patient has more than one gene mutation, risk estimates may be different, as this analysis does not account for possible interactions between gene mutations.

CANCER TYPE

C A N C E R R IS K

R IS K F O R G E N E R A L P O P U L AT IO N

R E L AT E D T O

1%-9%