1. CANCER GENETIC COUNSELING NORTH DAKOTA CANCER COALITION CANCER CONFERENCE MAY 18, 2011 Marie Schuetzle, MS, CGC Larissa Hansen, MS

2. 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

3. 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/

4. National Guidelines

5. 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

6. Clinical Guidelines

7. 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

8. Risk Assessment  Personal history  Family history  Pathological findings  National diagnostic/testing criteria  Mutation risk models  Genetic test results

9. No Hereditary Pattern

10. Possible Cancer Syndrome

11. 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

12. Cancer Syndrome Diagnosed

13. 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 II Same 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

14. Breast Cancer Example

15. 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

16. 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

23. Summary of Risk Estimates ModelMutation Risk BRCAPro4.6% Myriad2.6% Penn II21% patient 43% family

24. 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

25. Claus EB et al. Cancer 73:643,1994 Age% Risk 5915.7 6922.6 7927.4

26. 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

27. Informed Consent

28. Basic Elements of Informed Consent for Cancer Susceptibility Testing 1. 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 result 3. Possibility that the test will not be informative 4. Options for risk estimation without genetic or genomic testing 5. Risk of passing a genetic variant to children Modified from ASCO 2003 Statement

29. Basic Elements of Informed Consent for Cancer Susceptibility Testing 1. 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 result 3. Possibility that the test will not be informative 4. Options for risk estimation without genetic or genomic testing 5. Risk of passing a genetic variant to children Modified from ASCO 2003 Statement

30. Basic Elements of Informed Consent for Cancer Susceptibility Testing 1. 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 result 3. Possibility that the test will not be informative 4. Options for risk estimation without genetic or genomic testing 5. Risk of passing a genetic variant to children Modified from ASCO 2003 Statement

31. Basic Elements of Informed Consent for Cancer Susceptibility Testing 1. 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 result 3. Possibility that the test will not be informative 4. Options for risk estimation without genetic or genomic testing 5. Risk of passing a genetic variant to children Modified from ASCO 2003 Statement

32. Basic Elements of Informed Consent for Cancer Susceptibility Testing 1. 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 result 3. Possibility that the test will not be informative 4. Options for risk estimation without genetic or genomic testing 5. Risk of passing a genetic variant to children Modified from ASCO 2003 Statement

33. Basic Elements of Informed Consent for Cancer Susceptibility Testing 6. Technical accuracy of the test including, where required by law, licensure of the testing laboratory 7. 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

34. Basic Elements of Informed Consent for Cancer Susceptibility Testing 6. Technical accuracy of the test including, where required by law, licensure of the testing laboratory 7. 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

35. Basic Elements of Informed Consent for Cancer Susceptibility Testing 6. Technical accuracy of the test including, where required by law, licensure of the testing laboratory 7. 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

36. Basic Elements of Informed Consent for Cancer Susceptibility Testing 6. Technical accuracy of the test including, where required by law, licensure of the testing laboratory 7. 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

37. 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

38. 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

39. Basic Elements of Informed Consent for Cancer Susceptibility Testing 10. 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 testing Modified from ASCO 2003 Statement

40. Basic Elements of Informed Consent for Cancer Susceptibility Testing 10. 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 testing Modified from ASCO 2003 Statement

41. Basic Elements of Informed Consent for Cancer Susceptibility Testing 10. 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 testing Modified from ASCO 2003 Statement

42. Basic Elements of Informed Consent for Cancer Susceptibility Testing 10. 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 testing Modified from ASCO 2003 Statement

43. Basic Elements of Informed Consent for Cancer Susceptibility Testing 10. 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 testing Modified from ASCO 2003 Statement

44. Post-test Counseling

45. 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

46. 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

47. 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

48. Appropriate Referrals  Long term follow up programs  Clinicians/clinics for subsequent medical management

49. 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

50. Additional Testing Options  Other hereditary cancer syndromes indicated by personal or family history  Future discoveries/developments in the field of cancer genetics

51. QUESTIONS?

52. 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.

53. References  Schneider K. Counseling About Cancer. Strategies for Genetic Counseling, 2 nd 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