Understanding Your Positive Result. A guide to understanding your risk and taking action

Transcription

1 Understanding Your Positive Result A guide to understanding your risk and taking action

2 2017 Myriad Genetics, Inc. 320 Wakara Way, Salt Lake City, Utah PH: FX: PART ONE: Understanding Your Result Your test result may include three parts: your Genetic Test Result, your breast cancer riskscore (if applicable), and your Clinical History Analysis. Genetic Test Result A. Your Myriad myrisk Hereditary Cancer result summary is shown on the first page of your report. 1. Your myrisk Genetic Result is POSITIVE. This means that 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. A B C Myriad myrisk Hereditary Cancer Test myrisk Genetic Result RECEIVING HEALTHCARE PROVIDER Physician Name, MD Myriad Healthcare Partners 320 Wakara Way Salt Lake City, UT ORDERING PHYSICIAN: Physician Name, MD SPECIMEN Specimen Type: Buccal Draw Date: Aug 15, 2017 Accession Date: Aug 30, 2017 Report Date: Sept 4, 2017 GENE MUTATION INTERPRETATION MLH1 MYRISK GENETIC RESULT: POSITIVE clinically significant mutation identified c.133del (p.thr45glnfs*5) Heterozygous DETAILS ABOUT: MLH1 c.133del (p.thr45glnfs*5): NM_ ; AKA: 133delA ADDITIONAL FINDINGS: NO VARIANT(S) OF UNCERTAIN SIGNIFICANCE (VUS) IDENTIFIED PATIENT Name: Case Study 4 Date of Birth: Jan 1, 1980 Patient ID: 0000 Gender: Female Accession #: Requisition #: 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. HIGH CANCER RISK This patient has Lynch syndrome, Hereditary Non-Polyposis Colon Cancer (HNPCC). 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. 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. myrisk Genetic Result: Page 1 of 3 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 interventions should not be based on the VUS 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.

3 2017 Myriad Genetics, Inc. 320 Wakara Way, Salt Lake City, Utah PH: FX: D. You can find a list of all genes tested in the Genes Analyzed section. D myrisk Genetic Result ADDITIONAL INFORMATION GENES ANALYZED 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. Unless otherwise noted sequencing and large rearrangement analyses were Associated Cancer Risks and Clinical Management: Please see the myrisk performed on the following genes: Management Tool associated with this report for a summary of cancer risk and APC, ATM, BARD1, BMPR1A, BRCA1, professional society medical management guidelines that may be useful in developing a BRCA2, BRIP1, CDH1, CDK4, CDKN2A, plan for this patient based on test results and reported personal/family history, if CHEK2, EPCAM (large rearrangement only), applicable. Testing of other family members may assist in the interpretation of this MLH1, MSH2, MSH6, MUTYH, NBN, patient s test result. PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53. Sequencing was Analysis Description: The Technical Specifications summary (MyriadPro.com/myRisk) performed for select regions of POLE and describes the analysis, method, performance, nomenclature, and interpretive criteria of POLD1. and large rearrangement analysis this test. The classification and interpretation of all variants identified in this assay reflects was performed for select regions of GREM1 the current state of scientific understanding at the time this report was issued, and may (see technical specifications). change as new scientific information becomes available. The interpretation of this test **Other genes not analyzed with this test may be impacted if the patient has a hematologic malignancy or an allogeneic bone may also be associated with cancer. marrow transplant. 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. 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. E General Population This Patient 0 5 myrisk Genetic Result Breast Cancer riskscore Breast Cancer riskscore 23.6% RESULT: 23.6% Remaining Lifetime Risk for Breast Cancer 0.8% 5-Year Risk for Breast Cancer Average Risk BREAST CANCER RISKSCORE INTERPRETATION Breast Cancer riskscore - Remaining Lifetime Risk 20% Risk 2017 Myriad Genetics, Inc. 320 Wakara Way, Threshold Salt Lake City, Utah PH: FX: purposes of diagnosing, 13.1% counseling and treating the patient identified in the report and members of his or her family % 20 Above Average Risk >50 myrisk Genetic Result: Page 2 of 3 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. F. The Clinical and Cancer Family History Information Page displays the information regarding your clinical history and personal and cancer family history you reported. 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 ( 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 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 risk estimates. Clinical & Cancer Family History Information Please contact Myriad Medical Services at X 3850 to discuss any questions regarding this result. These test results should only be used in conjunction with the patient s clinical PATIENT CLINICAL HISTORY history SUMMARY and any previous analysis of appropriate family members. The patient s This Authorized Signature Benjamin B. Woman s Roa, PhD age clinical history and 37 test results should Hormone not be disclosed Replacement to a Therapy third party, (HRT) unless No pertains to this laboratory report: Diplomate ABMG Ancestry related to treatment or payment for treatment, without the patient s express White/Non-hispanic - HRT: Treatment type N/A Laboratory Director written authorization. It is strongly recommended that these results be communicated to 5 the 5 patient in a setting - HRT: that Current includes user appropriate counseling. No Height This test was developed and its performance characteristics determined by Weight Richard J. Wenstrup, MD 135 lbs. Laboratories. not - Number of years ago started been cleared or approved by N/A Myriad Genetic It has the U.S. Diplomate ABMG Age of menarche 12 Administration The - Additional years of intended use FDA has determined that clearance N/A Food and Drug (FDA). Chief Medical Patient s Officer menopausal status or approval for laboratory-developed Pre-menopausal tests - HRT: is not Past required. user No - Age of onset N/A - Number of years N/A ago ended Age of first live birth 24 Breast biopsy No 2017 Myriad Genetics, Inc. 320 Wakara Way, Salt Lake City, Utah PH: FX: purposes of diagnosing, counseling and treating the patient PERSONAL identified in / FAMILY the report CANCER and members HISTORY of his SUMMARY* or her family. myrisk AGE Genetic AT DIAGNOSIS Result: Page 3 of 3 registered trademarks of Myriad Genetics, Inc. in the United FAMILY States MEMBER and other jurisdictions. CANCER / CLINICAL 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 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 F Clinical & Family History Information: Page 1 of 1 If you have additional questions about your result please contact your healthcare provider. Myriad s Medical Services team is also available to help: (800) x3850 / helpmed@myriad.com

4 2017 Myriad Genetics, Inc. 320 Wakara Way, Salt Lake City, Utah PH: FX: PART TWO: Understanding Your Risk 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. myrisk Management Tool G. Cancers Associated with your positive myrisk Genetic Result. The top section of this report indicates that your genetic result is: POSITIVE. For cancer risks related to your myrisk Genetic Result, you will find a table of specific cancer risks based on your gene mutation. This table may include ranges of risks for these cancers as compared to the general population (see J.) Myriad myrisk Hereditary Cancer Test myrisk Management Tool RECEIVING HEALTHCARE PROVIDER SPECIMEN Physician Name, MD Specimen Type: Buccal Myriad Healthcare Partners Draw Date: Aug 15, Wakara Way Accession Date: Aug 30, 2017 Salt Lake City, UT Report Date: Sept 4, 2017 ORDERING PHYSICIAN: Physician Name, MD GENETIC TEST RESULTS SUMMARY INFORMATION MYRISK GENETIC RESULT: POSITIVE clinically significant mutation identified PATIENT Name: Case Study 4 Date of Birth: Jan 1, 1980 Patient ID: 0000 Gender: Female Accession #: Requisition #: Cancers on this table 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. A riskscore is only calculated for women under age 85, of soley European ancestry, and without a personal history of breast cancer, LCIS or atypical hyperplasia. 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. H I GENE MLH1 BREAST CANCER RISKSCORE at or above 20% 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. MUTATION c.133del (p.thr45glnfs*5) THIS GENETIC TEST RESULT IS ASSOCIATED WITH THE FOLLOWING CANCER RISKS: HIGH RISK: Gastric, Colorectal, Endometrial, Ovarian ELEVATED RISK: Pancreatic THIS RISKSCORE RESULT IS ASSOCIATED WITH THE FOLLOWING CANCER RISKS: ELEVATED RISK: Breast 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, Myriad Genetics, Inc. 320 Wakara Way, Salt Lake City, Utah PH: FX: Myriad, Myriad myrisk, riskscore, BRACAnalysis, myrisk COLARIS, myvision Medical and their Management respective logos are either trademarks or Name: Case Study 4 DOB: Jan 1, 1980 Accession #: myrisk Management Report Tool: Date: Page Sept 1 of 7 4, 2017 J 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. RISK FOR CANCER TYPE CANCER RISK RELATED TO GENERAL POPULATION SEBACEOUS NEOPLASMS To age 70 1%-9% <1.0% MLH1 SMALL BOWEL To age 70 3%-6% 0.1% MLH1 GASTRIC To age 70 6%-13% 0.3% MLH1 COLORECTAL To age 70 52%-82% 1.9% MLH1 ENDOMETRIAL To age 70 25%-60% 1.6% MLH1 OVARIAN To age 70 4%-12% 0.7% MLH1 HEPATOBILIARY TRACT To age %-4% 0.4% MLH1 PANCREATIC To age 70 1%-6% 0.5% MLH1 CENTRAL NERVOUS SYSTEM To age 70 1%-3% 0.4% MLH1 URINARY TRACT To age 70 1%-7% <1.0% MLH1 BREAST CANCER To age % 13% riskscore G myrisk Management Tool: Page 3 of 7

5 Family members should talk to their healthcare providers about hereditary cancer testing to help define their own risk and assist in the interpretation of this patient s genetic test results. This patient s relatives are at risk for carrying the same mutation(s) and associated cancer risks as this patient. Cancer risks for females and males 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 sisters have the highest chance of having the same mutation(s) as this patient. Other more distant relatives such as cousins, aunts, uncles, and grandparents also have a chance for carrying the same mutation(s). Testing of at-risk relatives can identify those family members with the same mutation(s) who may benefit from surveillance and early intervention. More resources for family testing are available at MySupport360.com. This patient has an estimated remaining lifetime risk of breast cancer greater than 20% based on riskscore, which includes both genetic and non-genetic factors that may be shared within the family. Female relatives of this patient may also be at a significantly increased risk for breast cancer and should consult with a healthcare provider to discuss their own risk. CANCER TYPE CANCER RISK RISK FOR GENERAL POPULATION FOR FEMALE RELATIVES OVARIAN To age 70 4%-12% 0.7% ENDOMETRIAL To age 70 25%-60% 1.6% FOR FEMALE AND MALE RELATIVES SEBACEOUS NEOPLASMS To age 70 1%-9% <0.1% SMALL BOWEL To age 70 3%-6% 0.1% URETER/RENAL PELVIS To age 70 1%-4% <1.0% GASTRIC To age 70 6%-13% 0.3% HEPATOBILIARY TRACT To age %-4% 0.4% PANCREATIC To age 70 1%-6% 0.5% COLORECTAL To age 70 52%-82% 1.9% CENTRAL NERVOUS SYSTEM To age 70 1%-3% 0.4% Please contact Myriad Professional Support at to discuss any questions regarding this result Myriad Genetics, Inc. 320 Wakara Way, Salt Lake City, Utah PH: FX: myrisk Management Tool: Page 7 of 7 Medical Management K myrisk Medical Management 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 management guidelines are summarized from established medical societies, primarily the National Comprehensive Cancer Network (NCCN). The reference cited should 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 a Tyrer-Cuzick risk estimate >20%, or multiple mutations in different genes), only the most aggressive management is shown. Only guidelines for the patient 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 require modification due to the patient s personal medical history, past surgeries and other treatments. Patients with a past history of cancer, benign tumors, or pre-cancerous findings may be candidates for long term surveillance and risk-reduction strategies beyond what is necessary for the treatment of their initial 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 made in consultation between each patient and his or her healthcare provider. FREQUENCY PROCEDURE AGE TO BEGIN (Unless otherwise RELATED TO indicated by fi ndings) SEBACEOUS NEOPLASMS Currently there are no specific medical management NA NA MLH1 guidelines for sebaceous neoplasm risk. SMALL BOWEL Consider upper endoscopy and/or capsule 1 endoscopy. 30 to 35 years Every 2 to 3 years MLH1 GASTRIC 1 Consider risk-reducing mastectomy 30 to 35 years Every 2 to 3 years MLH1 COLORECTAL Consider options for ovarian cancer chemoprevention 20 to 25 years, or individualized to a younger age based on the earliest Every 1 to 2 years MLH1 (i.e., oral contraceptives) 1 diagnosis in family URINARY TRACT Consider urinalysis. 30 to 35 years Annually MLH1 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. HEPATOBILIARY TRACT Currently there are no specific medical management guidelines for hepatobiliary cancer risk PANCREATIC Consider available options for pancreatic cancer screening, including the possibility of endoscopic ultrasonography (EUS) and MRI/magnetic resonance cholangiopancreatography (MRCP). It is recommended that patients who are candidates for pancreatic cancer screening be managed by a multidisciplinary team with experience in the screening for pancreatic cancer, preferably within research protocols. 2 NA NA MLH1 Individualized NA MLH1 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 Myriad Genetics, Inc. 320 Wakara Way, Salt Lake City, Utah PH: FX: myrisk Management Tool: Page 4 of 7 3 Since PART THREE: Information for Family Members you were found to have a genetic mutation, your relatives may want to consider genetic testing. 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 identified as above average using the 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. myrisk Medical Management INFORMATION FOR FAMILY MEMBERS CANCER RISK FOR MLH1 CLINICALLY SIGNIFICANT MUTATION END OF MYRISK MANAGEMENT TOOL.

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8 PATIENT SUPPORT Resources Your healthcare provider is always your number one resource. You are also invited to visit 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 x3850 to speak to a genetic counselor. Next Steps Working with your healthcare provider, the two of you will determine the appropriate next steps for you. Here are some possible actions to consider: 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 Hereditary Cancer Testing Provided by: Myriad Genetic Laboratories, Inc. 320 Wakara Way, Salt Lake City, UT Myriad, the Myriad logo, Myriad myrisk, the Myriad myrisk logo, riskscore the riskscore logo, mysupport360, and the mysupport360 logo are either trademarks or 2017, Myriad Genetic Laboratories, Inc. MRHCPOSPET / 7-17