CANCER GENETIC COUNSELINGNORTH DAKOTA CANCER COALITION CANCER CONFERENCEMAY 18, 2011

Marie Schuetzle, MS, CGC

Larissa Hansen, MS

Objectives

At the conclusion of this presentation, participants should be able to

Identify individuals at risk for hereditary cancer

Understand the cancer genetic counseling process

Recognize aspects of informed consent Be cognizant that medical management

will be addressed regardless of testing decisions

Genetic Counseling

Definition Genetic counseling is the process of helping people

understand and adapt to the medical, psychological and familial implications of genetic contributions to disease.

Degree Master of Science or Master of Arts in Genetic Counseling

granted by a genetic counseling program accredited by the American Board of Genetic Counseling (ABGC)

Certification Board eligible or board certified by the American Board

of Medical Genetics (ABMG) and the American Board of Genetic Counseling (ABGC)

http://www.nsgc.org/

National Guidelines

Indications for Genetic Evaluation Early age of onset Multiple primary cancers in one

individual Two + family members with the same or

related cancers Rare cancer Cancer diagnosis and high risk

population

Clinical Guidelines

Genetic Counseling Process

Assess hereditary cancer risk No hereditary pattern Suspicious of hereditary pattern, additional

evaluation needed Hereditary cancer syndrome, testing

warranted Offer testing when appropriate Facilitate testing when desired Provide recommendations

Risk Assessment

Personal history Family history Pathological findings National diagnostic/testing criteria Mutation risk models Genetic test results

No Hereditary Pattern

Possible Cancer Syndrome

Tumor Testing Criteria

Revised Bethesda Guidelines CRC diagnosis in a patient under 50 years of age Presence of synchronous/metachronous HNPCC-

associated tumors, regardless of age CRC with MSI-H histology diagnosed in a patient

under 60 years of age CRC diagnosed in a patient with >1 first-degree

relatives with an HNPCC-associated cancer, with one of the cancers diagnosed prior to age 50

CRC diagnosed in a patient with >2 first- or second-degree relatives with HNPCC-associated cancers, regardless of age

Umar et al, 2004

Cancer Syndrome Diagnosed

Diagnostic Criteria

Amsterdam Criteria I Three relatives with CRC, one is a first degree relative of

the other two At least two successive generations affected At least one of the relatives with CRC was diagnosed

prior to age 50 FAP is excluded Tumors verified via pathologic examination

Amsterdam Criteria IISame as above but insert “HNPCC-associated cancer (colorectal, endometrial, small bowel, ureter, renal pelvis)” in place of CRC in first and third bullets.

Vasen et al, 1991

Breast Cancer Example

Breast Cancer Example

First degree relative meeting national testing criteria:

Diagnosed at any age with 2 or more close blood relatives with breast or ovarian cancer diagnosed at any age.

Family member best to test.

www.nccn.org

Mutation Risk Models

BRCAPro Bayesian calculation taking into account first and second

degree relatives with breast and ovarian cancer, as well as those that are unaffected, tumor characteristics and oophorectomy

Myriad II Risks based on experiential data taking into account breast

and ovarian cancer in first and second degree relatives University of Pennsylvania

Risks factored from 966 families with 2 or more members with breast or ovarian cancer taking into account family history of pancreatic, prostate and male breast cancer as well

Summary of Risk Estimates

Model Mutation Risk

BRCAPro 4.6%

Myriad 2.6%

Penn II 21% patient43% family

Breast Cancer Risk Models

Gail Hormone history Breast cancer in first degree relatives Biopsy Race

Claus Family history of breast cancer

Tyrer-Cuzick (IBIS) Family history Hormone history AJ ancestry

Claus EB et al. Cancer 73:643,1994

Age % Risk

59 15.7

69 22.6

79 27.4

Genetic Counseling Process

Assess Hereditary Cancer Risk No Hereditary Pattern Suspicious of hereditary pattern, additional

evaluation needed Hereditary cancer syndrome, testing

warranted Offer testing when appropriate Facilitate testing when desired Provide Recommendations

Informed Consent

Basic Elements of Informed Consent for Cancer Susceptibility Testing1. Information on the specific genetic

mutation(s) or genomic variant(s) being tested, including whether the range of risk associated with the variant will impact medical care

2. Implications of a positive and negative result3. Possibility that the test will not be informative4. Options for risk estimation without genetic or

genomic testing5. Risk of passing a genetic variant to children

Modified from ASCO 2003 Statement

Basic Elements of Informed Consent for Cancer Susceptibility Testing1. Information on the specific genetic

mutation(s) or genomic variant(s) being tested, including whether the range of risk associated with the variant will impact medical care

2. Implications of a positive and negative result3. Possibility that the test will not be informative4. Options for risk estimation without genetic or

genomic testing5. Risk of passing a genetic variant to children

Modified from ASCO 2003 Statement

Basic Elements of Informed Consent for Cancer Susceptibility Testing1. Information on the specific genetic

mutation(s) or genomic variant(s) being tested, including whether the range of risk associated with the variant will impact medical care

2. Implications of a positive and negative result3. Possibility that the test will not be informative4. Options for risk estimation without genetic or

genomic testing5. Risk of passing a genetic variant to children

Modified from ASCO 2003 Statement

Basic Elements of Informed Consent for Cancer Susceptibility Testing1. Information on the specific genetic

mutation(s) or genomic variant(s) being tested, including whether the range of risk associated with the variant will impact medical care

2. Implications of a positive and negative result3. Possibility that the test will not be informative4. Options for risk estimation without genetic or

genomic testing5. Risk of passing a genetic variant to children

Modified from ASCO 2003 Statement

Basic Elements of Informed Consent for Cancer Susceptibility Testing1. Information on the specific genetic

mutation(s) or genomic variant(s) being tested, including whether the range of risk associated with the variant will impact medical care

2. Implications of a positive and negative result3. Possibility that the test will not be informative4. Options for risk estimation without genetic or

genomic testing5. Risk of passing a genetic variant to children

Modified from ASCO 2003 Statement

Basic Elements of Informed Consent for Cancer Susceptibility Testing6. Technical accuracy of the test including, where

required by law, licensure of the testing laboratory7. Fees involved in testing and counseling and, for

DTC testing, whether the counselor is employed by the testing company

8. Psychological implications of test results (benefits and risks)

9. Risks and protections against genetic discrimination by employers or insurers

Abbreviation: DTC, direct to consumer.Modified from ASCO 2003 Statement

Basic Elements of Informed Consent for Cancer Susceptibility Testing6. Technical accuracy of the test including, where

required by law, licensure of the testing laboratory7. Fees involved in testing and counseling and, for

DTC testing, whether the counselor is employed by the testing company

8. Psychological implications of test results (benefits and risks)

9. Risks and protections against genetic discrimination by employers or insurers

Abbreviation: DTC, direct to consumer.Modified from ASCO 2003 Statement

Basic Elements of Informed Consent for Cancer Susceptibility Testing6. Technical accuracy of the test including, where

required by law, licensure of the testing laboratory7. Fees involved in testing and counseling and, for

DTC testing, whether the counselor is employed by the testing company

8. Psychological implications of test results (benefits and risks)

9. Risks and protections against genetic discrimination by employers or insurers

Abbreviation: DTC, direct to consumer.Modified from ASCO 2003 Statement

Basic Elements of Informed Consent for Cancer Susceptibility Testing6. Technical accuracy of the test including, where

required by law, licensure of the testing laboratory7. Fees involved in testing and counseling and, for

DTC testing, whether the counselor is employed by the testing company

8. Psychological implications of test results (benefits and risks)

9. Risks and protections against genetic discrimination by employers or insurers

Abbreviation: DTC, direct to consumer.Modified from ASCO 2003 Statement

Genetic Information Nondiscrimination Act (GINA)

GINA & Health Insurance Illegal for health insurers to request, require, or

use genetic information to make decisions about: Your eligibility for health insurance Your health insurance premium, contribution amounts, or

coverage terms • Illegal for your health insurer to:

Consider family history or a genetic test result a pre-existing condition

Ask or require that you have a genetic test Use any genetic information they do have to discriminate

against you, even if they did not mean to collect it GINAhelp.org

GINA & Employment

Illegal for employers to use your genetic information in the following ways: To make decisions about hiring, firing, promotion,

pay, privileges or terms To limit, segregate, classify, or otherwise mistreat

an employee

• Illegal for an employer to request, require, or purchase the genetic information of a potential or current employee, or his or her family members.

GINAhelp.org

Basic Elements of Informed Consent for Cancer Susceptibility Testing10. Confidentiality issues, including, for DTC

testing companies, policies related to privacy and data security

11. Possible use of DNA testing samples in future research

12. Options and limitations of medical surveillance and strategies for prevention after genetic or genomic testing

13. Importance of sharing genetic and genomic test results with at-risk relatives so that they may benefit from this information

14. Plans for follow-up after testingModified from ASCO 2003 Statement

Basic Elements of Informed Consent for Cancer Susceptibility Testing10. Confidentiality issues, including, for DTC

testing companies, policies related to privacy and data security

11. Possible use of DNA testing samples in future research

12. Options and limitations of medical surveillance and strategies for prevention after genetic or genomic testing

13. Importance of sharing genetic and genomic test results with at-risk relatives so that they may benefit from this information

14. Plans for follow-up after testingModified from ASCO 2003 Statement

Basic Elements of Informed Consent for Cancer Susceptibility Testing10. Confidentiality issues, including, for DTC

testing companies, policies related to privacy and data security

11. Possible use of DNA testing samples in future research

12. Options and limitations of medical surveillance and strategies for prevention after genetic or genomic testing

13. Importance of sharing genetic and genomic test results with at-risk relatives so that they may benefit from this information

14. Plans for follow-up after testingModified from ASCO 2003 Statement

Basic Elements of Informed Consent for Cancer Susceptibility Testing10. Confidentiality issues, including, for DTC

testing companies, policies related to privacy and data security

11. Possible use of DNA testing samples in future research

12. Options and limitations of medical surveillance and strategies for prevention after genetic or genomic testing

13. Importance of sharing genetic and genomic test results with at-risk relatives so that they may benefit from this information

14. Plans for follow-up after testingModified from ASCO 2003 Statement

Basic Elements of Informed Consent for Cancer Susceptibility Testing10. Confidentiality issues, including, for DTC

testing companies, policies related to privacy and data security

11. Possible use of DNA testing samples in future research

12. Options and limitations of medical surveillance and strategies for prevention after genetic or genomic testing

13. Importance of sharing genetic and genomic test results with at-risk relatives so that they may benefit from this information

14. Plans for follow-up after testingModified from ASCO 2003 Statement

Post-test Counseling

Result Disclosure and Interpretation

Negative, Positive, Variant of Uncertain Significance (VUS)

Clarify the result in terms of personal and family history True negative vs. uninformative negative

Cancer Risk Assessment

Based on genetic test result, risk assessment models, or empiric data

Include basic risk assessments for family members when available and applicable

Cancer Screening Recommendations

Will be addressed regardless of result Individuals with negative test result but

increased cancer risk will receive individual screening recommendations

Discuss general American Cancer Society Guidelines for the Early Detection of Cancer

Appropriate Referrals

Long term follow up programs Clinicians/clinics for subsequent medical

management

Resource Provision

Pre-test and post-test genetic counseling medical record documentation provided to patient

Specialized resources: Provide template or custom letter to family

to explain testing results and implications to other family members

Psychosocial support Facing Our Risk of Cancer Empowered (FORCE) Bright Pink

Additional Testing Options

Other hereditary cancer syndromes indicated by personal or family history

Future discoveries/developments in the field of cancer genetics

QUESTIONS?

References

American Society for Clinical Oncology policy statement update. Genetic testing for cancer susceptibility. J Clin Oncol. 2003;21:2397–2406.

National Cancer Institute. NCI’s Community Cancer Centers Program (NCCCP). Cancer Genetic Counseling Assessment Tool. Available online at: http://ncccp.cancer.gov/.

National Comprehensive Cancer Network (2006) Clinical practice guidelines in oncology: colorectal cancer screening. www.nccn.org

Robson ME, Storm CD, Weitzel J, Wollins DS, Offit K. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol. 2010;28:893-901.

References

Schneider K. Counseling About Cancer. Strategies for Genetic Counseling, 2nd ed. New York: Wiley-Liss, 2002.

Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96:261–8.

Vasen HF, Mecklin JP, Khan PM, Lynch HT. The International Collaborative Group on hereditary non-polyposis colorectal cancer (ICG-HNPCC). Dis Colon Rectum. 1991;34:424–5