Understanding a - Amazon S3 · (if applicable), and your Clinical History Analysis. 1 Understanding...

Understanding a Positive Result

A guide to understanding risk and taking action

REPORT EXAMPLE

Integrated BRACAnalysis® with Myriad myRisk® Hereditary Cancer

myRisk Genetic ResultRECEIVING HEALTHCARE PROVIDERTest HCP, MDTest Medical Center123 Main StTestville, TX 55555

SPECIMENSpecimen Type: BloodDraw Date: Aug 02, 2018Accession Date: Aug 02, 2018Report Date: Aug 03, 2018

PATIENTName: Pt Last Name,

Pt First NameDate of Birth: Aug 02, 1981Patient ID: Patient idGender: FemaleAccession #: Requisition #:

GENETIC RESULT: POSITIVE - CLINICALLY SIGNIFICANT MUTATION IDENTIFIEDNote: "CLINICALLY SIGNIFICANT," as defined in this report, is a genetic change that is associated withthe potential to alter medical intervention.

BREAST CANCER RISKSCORETM: REMAINING LIFETIME RISK 20.0%This level of risk is at or above 20% threshold for consideration of modified medical management.See riskScoreTM Interpretation Section for more information.

CLINICAL HISTORY ANALYSIS: BEYOND THE GENETIC RESULT, NO MODIFIEDMANAGEMENT GUIDELINES IDENTIFIED BASED ON THE CLINICAL HISTORY PROVIDEDOther clinical factors may influence individualized management. This analysis may be incomplete if detailsabout cancer diagnoses, ages, family relationships or other factors were omitted or ambiguous.

GENE MUTATION INTERPRETATION

MLH1 c.XXXXXX Heterozygous

High Cancer RiskThis patient has Lynch syndrome/Hereditary Non-Polyposis ColorectalCancer (HNPCC).

DETAILS ABOUT: MLH1 c.XXXXXX: XXXXXX; (aka: XXXXXX)

Functional Significance: Suspected Deleterious - Abnormal Protein Production and/or FunctionThe heterozygous germline MLH1 mutation c.XXXXXX is located 3 nucleotides upstream of exon X. This mutation has been shown to segregate with cancer (Loader S et al. Genetic Testing 2005, 9:313-319; Myriad internal data), and shows strong association with more severe personal and family history of cancer, typical for individuals with an HNPCC-associated deleterious mutation (Myriad internal data; Goldgar DE et al, Hum Mutat, 2008, 29:1265-1272; Easton DF et al, Am J Hum Genet, 2007, 81:873-883).

Clinical Significance: High Cancer RiskThis mutation has been shown to segregate with cancer (Loader S et al. Genetic Testing 2005, 9:313-319; Myriad internal data), and shows strong association with more severe personal and family history of cancer, typical for individuals with an HNPCC-associated deleterious mutation (Myriad internal data; Goldgar DE et al, Hum Mutat, 2008, 29:1265-1272; Easton DF et al, Am J Hum Genet, 2007, 81:873-883). This mutation is associated with increased cancer risk and should be regarded as clinically significant.

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 anindividual's risk of cancer or other diseases. When identified, variants of uncertain significance (VUS) are reported. Likely benign variants (FavorPolymorphisms) and benign variants (Polymorphisms) are not reported and available data indicate that these variants most likely do not causeincreased cancer risk. Present evidence does not suggest that non-clinically significant variant findings be used to modify patient medicalmanagement beyond what is indicated by the personal and family history and any other clinically significant findings.

Variant Classification: Myriad's myVisionTM Variant Classification Program performs ongoing evaluations of variant classifications. In certaincases, healthcare providers may be contacted for more clinical information or to arrange family testing to aid in variant classification. When newevidence about a variant is identified and determined to result in clinical significance and management change, that information will automatically bemade available to the healthcare provider through an amended report.

myRisk Genetic Result: Page 1 of 3

© 2018 Myriad Genetics, Inc. | 320 Wakara Way, Salt Lake City, Utah 84108 | PH: 1-800-469-7423 FX: 801-584-3615The format and contents of this report are proprietary and may not be copied or used without permission, except for purposes ofdiagnosing, 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 MyriadGenetics, Inc. in the United States and other jurisdictions.

A. Your Myriad myRisk® Hereditary Cancer result

summary is located on the first page of your report.

It will look similar to the example shown to the right.

If you received an POSITIVE myRisk Hereditary

Cancer result it means:

1. Your myRisk Genetic Result is POSITIVE. You

tested positive for a mutation in one or more

genes. One or more of your genes that were

passed down through your family is altered,

or carries a genetic mutation, which increases

your risk for one or more hereditary cancers.

This mutation(s) is considered CLINICALLY

SIGNIFICANT and changes to your medical

management may be appropriate.

2. Your result may contain a breast cancer

riskScore®. If the riskScore was performed, details

will be provided on the following page of your

Genetic Test Result (see E.)

3. Your result will contain a Clinical History Analysis.

This analysis was based on personal clinical

risk factors and the cancer family history you

reported to your provider. If the analysis identified

any modified medical management, an orange

asterisk will appear. A summary of medical

management recommendations based on leading

medical society guidelines will be provided in the

myRisk Management Tool section of your report.

B. Your report provides you with detailed information

about your specific gene mutation and your

increased risk for associated cancers. With this

information, you and your healthcare provider can

develop a medical management plan that is right for

you.

C. In addition to your positive result, your testing

may have found one or more “Variants of Uncertain Significance (VUS).” A VUS is not currently known to

be associated with an increased cancer risk. Myriad

has made a lifetime commitment to understanding

the nature of these variants. If new evidence about

a variant is identified, that information will be made

available to your healthcare provider who will then

contact you with updated information. It is important

to understand that medical management decisions

should not be based on the VUS result.

A

C

B

Your test result may include three parts: your Genetic Test Result, your breast cancer riskScore®

(if applicable), and your Clinical History Analysis.

PART ONE:

1 Understanding a Positive Result

Genetic Test Result

Positive result with SINGLE SITE testing: If a member of your family has tested positive for a mutation, your provider may have ordered testing for only that mutation to see if you carry it. This is known as single site testing. If you get a positive single site test result, you DO carry the mutation that is in your family and should discuss relevant changes to your medical management with your healthcare provider. Because single site testing does not look for other mutations or assess risk from family history, there are limitations to the information. Positive results on single site tests will include a myRisk Management Tool that is specific ONLY to your gene mutation.

REPORT EXAMPLE

Name: DOB:Pt Last Name, Pt First Name Aug 02, 1981 Accession #: Report Date: Aug 03, 2018

ADDITIONAL INFORMATIONIndication for Testing: It is our understanding that this individual was identified fortesting due to a personal or family history suggestive of a hereditary predisposition forcancer.

Associated Cancer Risks and Clinical Management: Please see the "myRiskManagement Tool" associated with this report for a summary of cancer risk andprofessional society medical management guidelines that may be useful in developing aplan for this patient based on test results and reported personal/family history, ifapplicable. Testing of other family members may assist in the interpretation of thispatient's test result.

Analysis Description: The Technical Specifications summary (https://www.myriadpro.com/documents-and-forms/technical-specifications/) describes the analysis, method,performance, nomenclature, and interpretive criteria of this test. Current testingtechnologies are unable to definitively determine whether a variant is germline or somaticin origin, which may significantly impact risk estimates and medical management;therefore, these results should be correlated with this patient's personal and familyhistory. The interpretation of this test may also be impacted if the patient has ahematologic malignancy or an allogeneic bone marrow transplant.

GENES ANALYZED

Unless otherwise noted sequencing and largerearrangement analyses were performed on thefollowing genes:

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 wasperformed for select regions of POLE and POLD1,and large rearrangement analysis was performed forselect regions of GREM1 (see technicalspecifications).

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

CLASSIFICATION DISCLAIMER

THE CLASSIFICATION AND INTERPRETATION OF ALL VARIANTS IDENTIFIED IN THIS ASSAY REFLECTS THE CURRENT STATE OFMYRIAD'S SCIENTIFIC UNDERSTANDING AT THE TIME THIS REPORT WAS ISSUED. VARIANT CLASSIFICATION AND INTERPRETATIONMAY 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.



myRisk Genetic Result

© 2017 Myriad Genetics, Inc. | 320 Wakara Way, Salt Lake City, Utah 84108 | PH: 1-800-469-7423 FX: 801-584-3615The 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 identifi ed 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.

REPORT EXAMPLE

Breast Cancer riskScore™ - Remaining Lifetime Risk

General Population

This Patient

3530 40 45 >502520151050

20% Risk Threshold

13.1%

23.6%RESULT: 23.6% Remaining Lifetime Risk for Breast Cancer

0.8% 5-Year Risk for Breast Cancer

Breast Cancer riskScore™

23.6%

myRisk Genetic Result: of 3

Name: Case Study 4 DOB: Jan 1, 1980 Accession #: 00000000-000 Report Date: Sept 4, 2017

myRisk Genetic Result

Average Risk Above Average Risk

Breast Cancer riskScore™

These test results should only be used in conjunction with the patient’s clinical history and any previous analysis of appropriate family members. The patient’s clinical history and test results should not be disclosed to a third party, unless related to treatment or payment for treatment, without the patient’s express written authorization. It is strongly recommended that these results be communicated to the patient in a setting that includes appropriate counseling. This test was developed and its performance characteristics determined by Myriad Genetic Laboratories. It has not been cleared or approved by the U.S. Food and Drug Administration (FDA). The FDA has determined that clearance or approval for laboratory-developed tests is not required.

This Authorized Signature pertains to this laboratory report:

Benjamin B. Roa, PhDDiplomate ABMGLaboratory Director

Johnathan Lancaster, MDDiplomate ABMGChief Medical Offi cer

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

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 specifi c modifi ed 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 modifi ed 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 Specifi cations summary (https://www.myriadpro.com/documents-and-forms/technical-specifi cations/) describes the analysis, method, performance and interpretive criteria of this test. Data from 86 biomarkers are analyzed during NGS sequencing. The allele status of these markers is weighted and combined with patient clinical and family history data in the riskScore calculation. Clinical and 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 signifi cantly affect the provided breast cancer risk estimates.

© 2017 Myriad Genetics, Inc. | 320 Wakara Way, Salt Lake City, Utah 84108 | PH: 1-800-469-7423 FX: 801-584-3615The 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 identifi ed 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.

REPORT EXAMPLE

Name: Case Study 4 DOB: Jan 1, 1980 Accession #: 00000000-000 Report Date: Sept 4, 2017

Clinical & Cancer Family History Information

PERSONAL / FAMILY CANCER HISTORY SUMMARY*

FAMILY MEMBER CANCER / CLINICAL DIAGNOSIS AGE AT DIAGNOSIS

Patient None - -

Mother Colon 52

Maternal Aunt Ovarian 45

NUMBER OF PATIENT’S FEMALE RELATIVES

Daughters: 0 Sisters: 2 Maternal Aunts: 2 Paternal Aunts: 1

The clinical information displayed here was provided by a qualifi ed healthcare provider on the Test Request Form and other documents, and was not verifi ed 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 Specifi cations for Personal/Family History Analysis at https://new.myriadpro.com/documents-and-forms/technical-specifi cations/.

PATIENT CLINICAL HISTORY SUMMARY

Woman’s age 37 Hormone Replacement Therapy (HRT) No

Ancestry White/Non-hispanic - HRT: Treatment type N/A

Height 5’ 5” - HRT: Current user No

Weight 135 lbs. - Number of years ago started N/A

Age of menarche 12 - Additional years of intended use N/A

Patient’s menopausal status Pre-menopausal - HRT: Past user No

- Age of onset N/A - Number of years ago ended N/A

Age of fi rst live birth 24 Breast biopsy No

Clinical & Family History Information: Page 1 of 1

D. You can find a list of all the genes tested in the

Genes Analyzed section.

E. If the riskScore® was performed, this page of

your Genetic Test Result will contain details of

the analysis. This page displays an estimate of

your remaining lifetime risk for breast cancer as

well as your risk over the next five years. You can

compare your risk to the general population using

the graph provided.

If the analysis identified any modified medical

management based on your riskScore, an

orange asterisk will appear next to your

score. A summary of medical management

recommendations based on leading medical

society guidelines will be provided in the myRisk

Management Tool section of your report.

F. The Clinical and Cancer Family History Information Page displays the information

regarding your clinical history and personal and

cancer family history you reported.

D

REPORT EXAMPLE

myRisk Genetic ResultName: DOB:Pt Last Name, Pt First Name Aug 02, 1981 Accession #: Report Date: Aug 03, 2018

Breast Cancer riskScore®

Breast CancerriskScoreTM:

20.0%RESULT: 20.0% Remaining Lifetime Risk for Breast Cancer

0.7% 5-Year Risk for Breast Cancer

GeneralPopulation

ThisPatient

Breast Cancer riskScoreTM - Remaining Lifetime Risk20% RiskThreshold

Average Risk Above Average Risk

>

BREAST CANCER RISKSCORETM INTERPRETATION

The breast cancer riskScoreTM provides an estimate of the remaining lifetime risk for breast cancer. A risk estimate at or above 20% is associated withspecific modified medical recommendations, including consideration of more aggressive breast cancer screening and additional risk reductionmeasures. If applicable, details of these recommendations are provided in the accompanying myRisk Medical Management Tool or othersupplemental material. Women with a risk estimate below 20% may still be appropriate for consideration of modified medical management based onother clinical factors or estimates from other breast cancer risk models, such as Tyrer-Cuzick, Claus, and Gail.

BREAST CANCER RISKSCORETM ANALYSIS DESCRIPTION

The breast cancer riskScoreTM provides 5-year and remaining lifetime breast cancer risks, based on an analysis of genetic markers combined withpatient clinical and family history data. The Technical Specifications summary (https://www.myriadpro.com/documents-and-forms/technical-specifications/) describes the riskScoreTM eligibility criteria, analysis, method, performance and interpretive criteria of this test. Data from 86biomarkers are analyzed during next generation sequencing (NGS). The allele status of these markers is weighted and combined with patient clinicaland family history data in the riskScoreTM calculation. The Clinical and Cancer Family History Information section of this report displays the data usedfor this analysis and explains important limitations on the accuracy of riskScore (including significant over- or under-estimates of breast cancer risk)that can be caused by errors and/or omissions in the reported clinical and family history data.

TYRER-CUZICK BREAST CANCER RISK CALCULATIONREMAINING LIFETIME BREAST CANCER RISK: 11.5% 5-YEAR BREAST CANCER RISK: 0.4%

The National Comprehensive Cancer Network (NCCN) provides medical management recommendations for women with an estimated remaininglifetime breast cancer risk greater than 20% based on Tyrer-Cuzick. These recommendations are summarized on the myRisk Management Tool(MMT). If an MMT is not included with this report, current management recommendations from the NCCN Breast Cancer Screening and Diagnosispanel can be accessed at www.nccn.org. Version 7.02 of the Tyrer-Cuzick model was used for this risk estimate. Tyrer-Cuzick model Versions 7.02and 8.0 are available for download at the EMS-Trials website, http://www.ems-trials.org/riskevaluator.

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

This Authorized Signaturepertains to this laboratory report:

Benjamin B. Roa, PhDDiplomate ABMGLaboratory Director

Johnathan M. Lancaster, MD, PhDDiplomate ABOG, FACOG, FACSChief Medical Officer

These test results should only be used in conjunction with the patient's clinicalhistory and any previous analysis of appropriate family members. The patient'sclinical history and test results should not be disclosed to a third party, unlessrelated to treatment or payment for treatment, without the patient's express writtenauthorization. It is strongly recommended that these results be communicated tothe patient in a setting that includes appropriate genetic consultation. This test wasdeveloped and its performance characteristics determined by Myriad GeneticLaboratories. It has not been cleared or approved by the U.S. Food and DrugAdministration (FDA). The FDA has determined that clearance or approval forlaboratory-developed tests is not required.



E

If you have additional questions about your result please contact your healthcare provider. Myriad’s Medical Services team is also available to help:

(800) 469-7423 x3850 / [email protected]

REPORT EXAMPLE

Integrated BRACAnalysis® with Myriad myRisk® Hereditary CancerClinical & Cancer Family History Information

RECEIVING HEALTHCARE PROVIDERTest HCP, MDTest Medical Center123 Main StTestville, TX 55555


PATIENTName: Pt Last Name,

Pt First NameDate of Birth: Aug 02, 1981Patient ID: Patient idGender: FemaleAccession #: Requisition #:

PATIENT CLINICAL HISTORY SUMMARY

Woman's age 37

Ancestry White/Non-Hispanic

Height 5 ft 5 in

Weight 155 lbs

Age of menarche 12

Patient's menopausal status Pre-menopausal

- Age of onset N/A

Age of first live birth 24

Hormone Replacement Therapy (HRT) No

- HRT: Treatment type N/A

- HRT: Current user N/A

- Number of years ago started N/A

- Additional years of intended use N/A

- HRT: Past user N/A

- Number of years ago ended N/A

Breast biopsy Not Specified

PERSONAL / FAMILY CANCER HISTORY SUMMARY

FAMILY MEMBER CANCER / CLINICAL DIAGNOSIS AGE AT DIAGNOSIS

Patient Colorectal 37

Mother Colorectal 52

Aunt Maternal Ovarian 45

NUMBER OF PATIENT'S FEMALE RELATIVES

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 byMyriad. Family members listed as "other" are not included in a Tyrer-Cuzick breast cancer risk estimate or other personal/family history assessments. For moreinformation see the Specifications for Personal/Family History Analysis at https://www.myriadpro.com/documents-and-forms/technical-specifications/. The accuracy ofthe information provided in the Clinical and Cancer Family History Information section of the report may significantly affect the accuracy of breast cancer riskestimates provided based on either Tyrer-Cuzick or riskScoreTM.

riskScoreTM is only calculated for women who meet the eligibility criteria listed below. riskScoreTM is not valid, and may significantly over- or under-estimate breastcancer risk for a woman who does not meet these criteria: 1) ancestry is exclusively White/Non-Hispanic (includes Ashkenazi Jewish), 2) age is 85 or younger, 3) nopersonal history of breast cancer, LCIS, hyperplasia (with or without atypia), or a breast biopsy with unknown results, 4) no known mutation in a breast cancer riskgene has been found in the woman or any of her relatives, and 5) the sample was submitted with a current Test Request Form and the ordering healthcare providerhas not determined that riskScoreTM is inappropriate for the patient.

Clinical Information: Page 1 of 1


F

REPORT EXAMPLE

Integrated BRACAnalysis® with Myriad myRisk® Hereditary Cancer

myRisk Management ToolRECEIVING HEALTHCARE PROVIDERTest HCP, MDTest Medical Center123 Main StTestville, TX 55555


Name: Pt Last Name,Pt First Name

Date of Birth: Aug 02, 1981Patient ID: Patient idGender: FemaleAccession #: Requisition #:

PATIENT

GENETIC RESULT: POSITIVE - CLINICALLY SIGNIFICANT MUTATION IDENTIFIEDNote: "CLINICALLY SIGNIFICANT," as defined in this report, is a genetic change that is associated withthe potential to alter medical intervention.

BREAST CANCER RISKSCORETM: REMAINING LIFETIME RISK 20.0%This level of risk is at or above 20% threshold for consideration of modified medical management.See riskScoreTM Interpretation Section for more information.

CLINICAL HISTORY ANALYSIS: BEYOND THE GENETIC RESULT, NO MODIFIEDMANAGEMENT GUIDELINES IDENTIFIED BASED ON THE CLINICAL HISTORY PROVIDEDOther clinical factors may influence individualized management. This analysis may be incomplete if detailsabout cancer diagnoses, ages, family relationships or other factors were omitted or ambiguous.

THIS GENETIC TEST RESULT IS ASSOCIATED WITH THEFOLLOWING CANCER RISKS:

HIGH RISK: Colorectal, Endometrial, Ovarian, Gastric

ELEVATED RISK: Pancreatic

GENE MUTATION

MLH1 c.XXXXXX Heterozygous

BREAST CANCER RISKSCORETM THIS BREAST CANCER RISKSCORETM IS ASSOCIATED WITHTHE FOLLOWING CANCER RISKS:

At or above 20% ELEVATED RISK: Female Breast

Please see the Genetic Test Result for more details on any variant(s) detected in this patient, including variant classification information.

ADDITIONAL FINDINGS: NO VARIANT(S) OF UNCERTAIN SIGNIFICANCE (VUS) IDENTIFIED

TYRER-CUZICK BREAST CANCER RISK CALCULATION

REMAINING 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 amutation in a gene associated with breast cancer risk, age is 85 or older, if the sample was submitted with a version of the Test Request Form thatdoes not include all of the fields required to collect the clinical information used in the calculation, or if the provider indicates on the Test RequestForm that the Tyrer-Cuzick calculation is not appropriate for the patient. 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.

myRisk Management Tool: Page 1 of 8


REPORT EXAMPLE

myRisk Management ToolName: DOB: Report Date:Pt Last Name, Pt First Name Aug 03, 2018Aug 02, 1981 Accession #:

CANCER TYPE CANCER RISKRISK FOR

GENERAL POPULATION RELATED TO

Risk for a second Lynch-related cancer after a firstcancer diagnosis

Increased risk NA MLH1

OVERALL CANCER RISK (LYNCH CANCERS)

To age 70 4%-12% 0.7% MLH1

OVARIAN

To age 70 6%-13% 0.4% MLH1

GASTRIC

To age 70 3%-6% 0.1% MLH1

SMALL BOWEL

To age 70 5%-7% 0.7% MLH1

URINARY TRACT

To age 70 1%-6% 0.5% MLH1

PANCREATIC

To age 70 1.4%-4% 0.5% MLH1

HEPATOBILIARY TRACT

To age 70 1%-3% 0.4% MLH1

CENTRAL NERVOUS SYSTEM

To age 70 1%-9% <1.0% MLH1

SEBACEOUS NEOPLASMS

Current age to age 85 20.0% 13.1% riskScoreTM at or above the20% threshold

FEMALE BREAST



Your future risk of cancer is influenced by your Genetic Test Result, your personal clinical

history and your family history of cancer. The myRisk Management Tool provides a

summary of your future risks based on your genetic result and the information provided

to Myriad, but additional risk factors should be discussed with your provider.

G. Cancers Associated with a Positive myRisk Genetic Result. If you received a Positive myRisk® Genetic

Result, you will find a table of cancer risks specific to

your gene mutation on the first page of the myRisk

Management Tool below the genetic test result

summary information. An additional table may include

ranges of risks for these cancers as compared to the

general population (see J.)

Cancers on these tables may be in red or orange. Red

indicates that the increase in risk is significantly more

than the general population. Orange indicates that

the risk is elevated and there may not be an exact

percentage known at this time.

H. You may receive a riskScore®. riskScore is only

calculated for women under age 85, of solely White

/ Non-Hispanic and/or Ashkenazi Jewish ancestry,

without a personal history of breast cancer, LCIS,

hyperplasia, atypical hyperplasia, or a breast biopsy

with unknown results. This score is calculated using

both genetic and non-genetic factors that may be

shared within your family. It is important to note that

if your genetic mutation has an increase in risk for

breast cancer, then your breast cancer risk will be

defined only by your myRisk Genetic Result. However

if your gene mutation is not known to carry a risk for

breast cancer, then your healthcare provider may use

riskScore to understand your risk for breast cancer.

If your riskScore is calculated to be 20% or higher,

modified medical management recommendations will

be summarized later in the report.

I. If you are a woman who has never been diagnosed

with breast cancer and have no relatives with a known

genetic mutation you will also receive a Tyrer-Cuzick Risk Calculation. Tyrer-Cuzick is a model used to

predict a woman’s risk of developing breast cancer

which was developed by leading researchers. Tyrer-

Cuzick takes into consideration your family history

of cancer and other personal clinical risk factors. If

your Tyrer-Cuzick Risk Calculation is 20% or higher,

modified medical management recommendations will

be summarized later in the report.

G

H

I

PART TWO:

2

myRisk Management Tool

3

J

Understanding a Positive Result

REPORT EXAMPLE

myRisk Management ToolName: DOB:Pt Last Name, Pt First Name Aug 02, 1981 Accession #: Report Date: Aug 03, 2018

WHAT MANAGEMENT FOR CANCER RISKS SHOULD BE CONSIDERED?This overview of clinical management guidelines is based on the patient's personal and family history and genetic test results. Medical managementguidelines are summarized from established medical societies, primarily the National Comprehensive Cancer Network (NCCN). The reference citedshould always be consulted for more details. If management for a specific cancer (e.g. breast) is available due to multiple causes (e.g. a mutation and aTyrer-Cuzick risk estimate >20%, or multiple mutations in different genes), only the most aggressive management is shown. Only guidelines for thepatient's long-term care related to cancer prevention are included.

No information is provided related to treatment of a previous or existing cancer or polyps. The recommendation summaries below may requiremodification due to the patient's personal medical history, past surgeries and other treatments. Patients with a past history of cancer, benign tumors, orpre-cancerous findings may be candidates for long term surveillance and risk-reduction strategies beyond what is necessary for the treatment of theirinitial diagnosis. Any discussion of medical management options is for general information purposes only and does not constitute a recommendation.While genetic testing and medical society recommendations provide important and useful information, medical management decisions should be madein consultation between each patient and his or her healthcare provider.

PROCEDURE AGE TO BEGINFREQUENCYUnless otherwise

indicated by findingsRELATED TO

Colonoscopy4,5 20 to 25 years, or 2 to 5 yearsyounger than the earliest

diagnosis in family if it is underage 25

Every 1 to 2 years MLH1

Colorectal surgical evaluation may be appropriate forsome patients5

Individualized NA MLH1

Consider the use of aspirin as a risk-reduction agent4,5 Individualized Individualized MLH1

COLORECTAL

Patient education about endometrial cancer symptoms.5 Individualized NA MLH1

Consider pelvic examination, endometrial samplingand transvaginal ultrasound.4,5

30 to 35 years Annually MLH1

Consider hysterectomy.4,5 After completion of childbearing NA MLH1

ENDOMETRIAL

Consider bilateral salpingo-oophorectomy.4,5 Age 40 or after completion ofchildbearing

NA MLH1

Consider transvaginal ultrasound and CA-125measurement.4,5

30 to 35 years NA MLH1

Consider options for ovarian cancer risk-reductionagents (i.e. oral contraceptives).1,5

Individualized NA MLH1

Patient education about ovarian cancer symptoms5 Individualized NA MLH1

OVARIAN



REPORT EXAMPLE

myRisk Management ToolName: DOB:Pt Last Name, Pt First Name Aug 02, 1981 Accession #: Report Date: Aug 03, 2018

• Risk estimates based on provider-supplied information. Some of the risk estimates and management recommendation summaries provided inthis report are based on our interpretation of information supplied by the ordering health care provider on the test request form (seeSpecifications for Personal/Family History analysis at https://myriadpro.com/documents-and-forms/technical-specifications/). The patient'sactual risks and appropriate management may be significantly different if details provided for cancer diagnoses, ages, family relationships orother factors were incorrect, omitted, ambiguous or have since changed. Please review the clinical history listed on the Clinical & Family HistoryInformation page of this report to make sure that the information used was provided and interpreted correctly.

• Variability in Tyrer-Cuzick risk estimates. Tyrer-Cuzick estimates of breast cancer risk can vary significantly based on the way in which themodel is used, and the estimate provided here may be higher or lower than what would be calculated by other users. For complete details ofhow Myriad calculates Tyrer-Cuzick risk estimates, including how Myriad handles information provided in a format not compatible with themodel, please see the Specifications for Personal/Family History analysis at https://myriadpro.com/documents-and-forms/technical-specifications/). These Specifications also include information for recalculating the Tyrer-Cuzick breast cancer risk estimate if desired.

• What is meant by "High Risk" and "Elevated Risk"? In the Genetic Test Result Summary, a gene-associated cancer risk is described as "HighRisk" for a cancer type if all of the following conditions are met: the absolute risk of cancer is approximately 5% or higher, the increase in riskover the general population is approximately 3-fold or higher, and there is significant data from multiple studies supporting the cancer riskestimate. A gene is described as "Elevated Risk" for a cancer type if there is sufficient data to support an increase in cancer risk over thegeneral population risk, but not all criteria for "High Risk" are met.

INFORMATION FOR FAMILY MEMBERSFamily members should talk to their healthcare providers about hereditary cancer testing to help define their own risk and assist in the interpretation ofthis patient's genetic test result.

• This patient's relatives are at risk for carrying the same mutation(s) and associated cancer risks as this patient. Cancer risks for females andmales who have this/these mutation(s) are provided below.

• Family members should talk to a healthcare provider about genetic testing. Close relatives such as parents, children, brothers, and sistershave the highest chance of having the same mutation(s) as this patient. Other more distant relatives such as cousins, aunts, uncles, andgrandparents also have a chance for carrying the same mutation(s). Testing of at-risk relatives can identify those family members with the samemutation(s) who may benefit from surveillance and early intervention. More resources for family testing are available at MySupport360.com.

• In rare instances, an individual may inherit mutations in both copies of the MLH1 gene, leading to the condition Constitutional Mismatch Repair-Deficiency syndrome (CMMR-D). Individuals with CMMR-D often have significant complications in childhood, including colorectal polyposis anda high risk for colorectal, small bowel, brain, and hematologic cancers. Individuals with CMMR-D often have café-au-lait spots. The children ofthis patient are at risk of inheriting CMMR-D only if the other parent is also a carrier of a MLH1 mutation. Screening the spouse/partner of thispatient for MLH1 mutations may be appropriate.

• Parents who are concerned about the possibility of passing on an MLH1 mutation to a future child may want to discuss options for prenataltesting and assisted reproduction techniques, such as pre-implantation genetic diagnosis (PGD).

• This patient has an estimated remaining lifetime risk of breast cancer at or above the 20% threshold based on the breast cancer riskScoreTM

estimate, which includes both genetic and non-genetic factors that may be shared within the family. Female relatives of this patient may also beat a significantly increased risk for breast cancer and should consult with a healthcare provider to discuss their own risk.

CANCER RISK FOR MLH1 CLINICALLY SIGNIFICANT MUTATIONCANCER TYPE CANCER RISK RISK FOR GENERAL POPULATION

FOR FEMALE RELATIVES

To age 70 1.7%25%-60%

ENDOMETRIAL

To age 70 0.7%4%-12%

OVARIAN

FOR MALE RELATIVES

To age 80 10.9%Elevated Risk

PROSTATE



It is important to share information about your test

results with your family. They may want to talk with

a healthcare provider about how this affects them

and the possibility of genetic testing. The Medical

Management Tool shows risk levels associated with

your gene mutation for family members.

If your risk of breast cancer was estimated to be

above average using riskScore®, your female relatives

may also be at an increased risk for breast cancer.

Your relatives may want to consult with a healthcare

provider to discuss their possible risk.

K

Medical Management

Information for Family MembersPART THREE:3If you were found to have a genetic mutation, your relatives

may want to consider genetic testing.

K. The myRisk Medical Management Tool provides a

summary of management recommendations from leading

medical societies that you and your healthcare provider

may consider. In general, changes to your cancer risk

management can take four possible directions:

1. You may be screened more often and perhaps with

different or additional tests than you have had

previously.

2. It might also be recommended that you take

medications (known as risk-reducing agents) to

reduce your risk.

3. There may be surgical steps to discuss.

4. You may discuss lifestyle changes with your provider.

Your healthcare provider will work with you to determine

the best medical management plan for you. Be sure to

contact your healthcare provider on a regular basis for

updated information.

Notes

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Hereditary Cancer Testing Provided by: Myriad Genetic Laboratories, Inc. 320 Wakara Way, Salt Lake City, UT 84108

Myriad, the Myriad logo, Myriad myRisk, the Myriad myRisk logo, riskScore the riskScore logo, mySupport360, and the mySupport360 logo are either trademarks

or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions. ©2017, Myriad Genetic Laboratories, Inc. MRHCPOSPET / 7-17

Next Steps

Schedule any follow-up appointments

Speak with your family members about your result and encourage them to see their healthcare provider about cancer prevention and testing

Consider speaking with a genetic counselor about your test result and family history

Working with your healthcare provider, the two of you will determine the appropriate next steps for you. Here are some possible actions to consider:

Hereditary Cancer Testing Provided by: Myriad Genetic Laboratories, Inc. 320 Wakara Way, Salt Lake City, UT 84108

Myriad, the Myriad logo, Myriad myRisk, the Myriad myRisk logo, riskScore the riskScore logo, mySupport360, and the mySupport360 logo are either trademarks

or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions. ©2018, Myriad Genetic Laboratories, Inc. MRHCPOSPET / 7-18

Your healthcare provider is always your number one resource. You are also

invited to visit www.mySupport360.com, the Myriad program offering

information and support for patients. You will find valuable information that will

help you better understand your test result, and you can join a community of

people who are on the same hereditary cancer testing journey as you.

You may also contact Myriad’s Medical Services team at 1-800-469-7423 x3850

to speak to a genetic counselor.

ResourcesPATIENT SUPPORT

Understanding a - Amazon S3 · (if applicable), and your Clinical History Analysis. 1 Understanding...

Documents

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