GenetiKit Workshop Given by: Dr. Sean Blaine, Family Physician Dr. June Carroll, Family Physician Clare Gibbons, Genetic Counsellor Cathy Gilpin, Genetic Counsellor Funded by CIHR

2 GenetiKit Project  Purpose:  To help family physicians think “genetically”  To increase knowledge about genetic testing for common disorders  To give family physicians a framework for assessing the usefulness of new genetic tests Funded by CIHR

3 GenetiKit Project Protocol Step 1: Questionnaire #1 – already completed Step 2: Workshop  Introduce tools to help integrate genetics into practice - case example Step 3: Use project tools over next 6 months Step 4: Questionnaire #2  $250 to compensate for your time at completion of Q2 We want to see:  What you think of our project materials  Do they help you in practice? Please do not share this information with your colleagues

4  Why is genetics important?  Case example  GenetiKit tools  Study protocol  Gene Messenger  GenetiKit Web site Workshop Outline

5  By 2010:  Predictive genetic tests for a dozen common conditions  “$1000 genome sequencing test”  No longer only the domain of geneticists and genetic counsellors Genomic medicine will change medical practice

6 The Promise of Genetics:  Prediction of risk of disease  Individualized screening, surveillance, and prevention  Safer and more effective drug therapy  Individualized environmental risk factor assessment

7 The reality – Is this “genohype”?  Genetic testing available for very few common adult onset hereditary diseases  Gene-environment interaction responsible for most common diseases  Lack of evidence for effective interventions

8 Why should family physicians know about genetics?  Common diseases  Public interest  Media coverage of genetic testing  Direct marketing of genetic testing  Patients will turn to family physicians for information and advice

FP’s patients asked: Where would you go for more information about genetic testing? Carroll, Blaine et al 2002 Unpublished data

10 What Makes Genetic Testing for Adult-Onset Diseases Different from Other Types of Testing?  Uncertainty  Will the condition develop?  When?  How severe?  Will interventions make a difference?  Direct implications for family members  Ethical, legal and social issues

11 Case Example - Breast Cancer  35 year old investment banker  asked her busy family doctor to refer her for genetic testing  history of breast cancer in grandmother  has heard of BRCA testing  looked at Myriad website  would like genetic testing…..

12 Maternal family history 32 David A&W 35 PATIENT A&W Breast Ca Dx 72 Breast Legend 60 Irene A&W 58 Jean ↑ Chol Michael Jason A&W 76 d. MI 63 George HTN

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Family history assessment Breast Legend

15 Family history assessment Breast Legend

16 Family history assessment Breast Legend

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18 Ontario Physician’s Guide to Referral of Patients with a Family History of Cancer to a Familial Cancer Genetics Clinic or Genetics Clinic Sources:  MOH 2002 Bulletin gram/ohip/bulletins/4000/bul4381.html  Ontario Medical Review (Nov 2001)

21 Let’s continue the case….

22 Pearls – Red flags for hereditary disorders  Multiple affected relatives  More than 1 generation affected  Closely related  Early age of onset

23 Who should be offered referral for genetic counselling and/or genetic testing?  Multiple cases of breast and/or ovarian cancer in family  closely related relatives  more than one generation  Br Ca diagnosed at < age 50  Breast cancer diagnosed at age < 35  Family member with both breast and ovarian cancers  Ashkenazi Jewish + relatives with breast or ovarian cancer

24 Who should be offered referral for genetic counselling and/or genetic testing?…  Family member with primary cancer in both breasts  especially if diagnosed < age 50  Family member with invasive serous ovarian cancer  Male breast cancer  Family member with an identified BRCA1 or BRCA2 mutation

25 Adding paternal family history 32 David A&W 35 PATIENT A&W Breast Ca Dx Irene A&W 58 Jean ↑ Chol Michael Jason A&W 76 d. MI 63 George HTN Ovarian Ca Dx ? Bilateral Breast Ca Dx ? Breast Ovarian Legend

26 32 David A&W 35 PATIENT A&W Breast Ca Dx Irene A&W 58 Jean ↑ Chol Michael Jason A&W 76 d. MI 63 George HTN Ovarian Ca Dx ? Bilateral Breast Ca Dx ? Breast Ovarian Legend Diabetes Paternal family history

27 32 David A&W 35 PATIENT A&W Breast Ca Dx Irene A&W 58 Jean ↑ Chol Michael Jason A&W 76 d. MI 63 George HTN d. 57 Ovarian Ca Dx 56 Breast Ovarian Legend Diabetes Bilateral Breast Ca Dx 45 Dx ? A&W d. 70’s Breast Ca Dx 69 90’s A&W Paternal family history

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29 Breast Ovarian Legend 32 David A&W 35 PATIENT A&W Breast Ca Dx Irene A&W 58 Jean ↑ Chol Michael Jason A&W 76 d. MI 63 George HTN Ovarian Ca Dx 56 Diabetes Bilateral Breast Ca Dx 45 Dx ? A&W 90’s A&W d. 70’s Breast Ca Dx 69 Family history

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31 Family history assessment Breast Ovarian Legend

32 bb BbBb BbBb BbBb Breast Cancer Affected with breast cancer Autosomal Dominant Inheritance Population Risk Population Risk Susceptible BRCA gene Unaffected Legend B: BRCA gene with mutation b: normal BRCA gene

33 Consequences of having a BRCA mutation Estimated Risk in BRCA Mutation Carriers – by Age 70 In General Population Breast Cancer ♀ %11% Ovarian Cancer BRCA %1-2% Ovarian Cancer BRCA %1-2% Breast Cancer ♂ BRCA2 6%<1%

34 Breast Ovarian Legend 32 David A&W 35 PATIENT A&W Breast Ca Dx Irene A&W 58 Jean ↑ Chol Michael Jason A&W 76 d. MI 63 George HTN Ovarian Ca Dx 56 Diabetes Bilateral Breast Ca Dx 45 Dx ? A&W 90’s A&W d. 70’s Breast Ca Dx 69 Family history

35 Possible Genetic Testing Results

36 Possible Genetic Testing Results

37 Possible Genetic Testing Results

38 Possible Genetic Testing Results

39 What are the benefits / harms of genetic testing for hereditary breast/ovarian cancer?

40 BENEFITS - Mutation Present  Disease Causing Mutation Present  Gene mutation predicted to cause or increase risk for disease  Clinical Benefit  Clear basis for existing clinical interventions that improve outcome  “OK, so I have the gene, what should I do to protect myself and stay healthy?”

41 BENEFITS - Mutation Absent  Clear Negative Genetic Test Result  Absence of a known gene mutation previously identified in the family  Emotional Benefit  Relief from worry about disease risk  “Thank goodness I don’t have it!”

42 Benefits

43 HARMS – Mutation Present  Disease Causing Mutation Present Socio-legal Harms  Insurance premiums may be increased  Other Harms Fear!  Patient may become fatalistic towards health  Other family members may become distressed on patient’s or their own behalf

44 HARMS – Mutation Present  Variant of Unknown Significance  Emotional harm Uncertainty  What does the mutation really mean? How to handle it?  Remember they are still at high risk on the basis of their family history, so the clinical interventions apply and may carry their own risks

45 HARMS – Mutation Absent  Clear Negative gene test result  Emotional harm Survivor Guilt  Cannot identify with the disease group  No excuse for life problems

46 HARMS - Mutation Absent  Uninformative Test Result  Health Behaviour Harm  Complacency  Fatalism towards health  Still need to follow clinical recommendations as family history risk still present

47 Harms

48 What can be done for BRCA Mutation Carriers to reduce the risk of breast/ovarian cancer? Surgical options - Bilateral risk-reducing mastectomy - Bilateral risk-reducing oophorectomy - 90% risk reduction in high-risk women - hazard ratio for br ca = hazard ratio for ovarian ca = 0.04 Chemoprevention -Tamoxifen - raloxifene, aromatase inhibitors - shows promise in BRCA2 carriers - under study

49 Genetics clinical pathway  Pattern – is it genetic?  Known gene mutation(s) for disorder?  Evidence for gene mutation = disorder?  What proportion of people with the disorder have the gene mutation?  Can we change disease incidence?  Can we change disease outcome?

50 Genetic Clinic Resources  Talk to your local genetics clinic  Check whether referral appropriate  Update on new genetic tests or advancements  Contact information in package

51 Family Physician’s Role in Genetics  Take a family history  Assess risk  Refer to genetics  Discuss benefits and harms of genetic testing  Provide emotional support  Coordinate prevention and management

52 GenetiKit Tools  Hereditary breast/ovarian cancer triage/management card + patient booklet and web site  Hereditary crc triage/management card  Pearls  Ontario Guidelines for referral and testing for hereditary breast/ovarian and colorectal cancer  Family History Tool  Consequences tool  Gene Messenger  Contact sheet for genetic clinic referrals

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54 Gene Messenger  To suggest topics, us at: 

55 GenetiKit Web Site Password: genetics

56 Please fill in the workshop evaluation Thank you. Questions?