Transcript Hereditary Breast Cancer - Welcome

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
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
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Funded by CIHR
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
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Workshop Outline
Why
is genetics important?
Case example
GenetiKit tools
Study protocol
 Gene
Messenger
 GenetiKit Web site
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Genomic medicine will change
medical practice
 By
2010:
 Predictive genetic tests for a dozen
common conditions
 “$1000 genome sequencing test”
 No longer only the domain of geneticists and
genetic counsellors
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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
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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
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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
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FP’s patients asked: Where would you go for
more information about genetic testing?
FP
Internet
Cancer Sp
Gen Coun
Books
Geneticist
Fam mem
Magazines
Surgeon
0
20
40
60
80
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Carroll, Blaine et al 2002 Unpublished data
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
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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…..
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Maternal family history
Legend
Breast
76
d. MI
63
George
HTN
35
PATIENT
A&W
60
Irene
A&W
32
David
A&W
Breast Ca
Dx 72
58
Jean
↑ Chol
30
Michael
A&W
30
Jason
A&W
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Legend
Breast
Family history
assessment
Legend
Breast
Family history
assessment
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Legend
Breast
Family history
assessment
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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
http://www.health.gov.on.ca/english/providers/pro
gram/ohip/bulletins/4000/bul4381.html
Ontario
Medical Review (Nov 2001)
www.oma.org/pcomm/OMR/nov/01genetics.htm
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Let’s continue the case….
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Pearls – Red flags for hereditary
disorders
 Multiple
affected relatives
 More than 1 generation affected
 Closely related
 Early age of onset
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Who should be offered referral for genetic counselling
and/or genetic testing?
 Multiple

closely related relatives

more than one generation

Br Ca diagnosed at < age 50
 Breast
cancer diagnosed at age < 35
 Family

cases of breast and/or ovarian cancer in family
member with both breast and ovarian cancers
Ashkenazi Jewish + relatives with breast or ovarian cancer
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Who should be offered referral for genetic counselling
and/or genetic testing?…
 Family
member with primary cancer in both breasts
 especially
 Family
if diagnosed < age 50
member with invasive serous
ovarian cancer
 Male
breast cancer
 Family
member with an identified
BRCA1 or BRCA2 mutation
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Adding paternal family history
Legend
76
d. MI
Ovarian Ca
Dx ?
Bilateral
Breast Ca
Dx ?
63
George
HTN
35
PATIENT
A&W
60
Irene
A&W
32
David
A&W
Breast
Ovarian
Breast Ca
Dx 72
58
Jean
↑ Chol
30
Michael
A&W
30
Jason
A&W
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Paternal family history
Legend
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d. MI
Ovarian Ca
Dx ?
Bilateral
Breast Ca
Dx ?
Diabetes
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George
HTN
35
PATIENT
A&W
60
Irene
A&W
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David
A&W
Breast
Ovarian
Breast Ca
Dx 72
58
Jean
↑ Chol
30
Michael
A&W
30
Jason
A&W
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Paternal family history
Legend
Breast
90’s
A&W
d. 57
Ovarian Ca
Dx 56
A&W
Bilateral
Breast Ca
Dx 45
Dx ?
Diabetes
d. 70’s
Breast Ca
Dx 69
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George
HTN
35
PATIENT
A&W
76
d. MI
60
Irene
A&W
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David
A&W
Ovarian
Breast Ca
Dx 72
58
Jean
↑ Chol
30
Michael
A&W
30
Jason
A&W
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Family history
Legend
Breast
90’s
A&W
Ovarian Ca
Dx 56
A&W
Bilateral
Breast Ca
Dx 45
Dx ?
Diabetes
d. 70’s
Breast Ca
Dx 69
63
George
HTN
35
PATIENT
A&W
76
d. MI
60
Irene
A&W
32
David
A&W
Ovarian
Breast Ca
Dx 72
58
Jean
↑ Chol
30
Michael
A&W
30
Jason
A&W
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Family history
assessment
Legend
Breast
Ovarian
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Autosomal Dominant Inheritance
Legend
Unaffected
Bb
bb
Bb
Affected with
breast cancer
B: BRCA gene
with mutation
Breast Cancer
bb
Population
Risk
b: normal BRCA
gene
Bb
bb
Susceptible
BRCA gene
Population
Risk
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Consequences of having a BRCA mutation
Estimated Risk in
BRCA Mutation
Carriers
In General
Population
– by Age 70
Breast Cancer ♀
50 - 85%
11%
Ovarian Cancer
40-60%
1-2%
10-20%
1-2%
6%
<1%
BRCA1
Ovarian Cancer
BRCA2
Breast Cancer ♂
BRCA2
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Family history
Legend
Breast
90’s
A&W
Ovarian Ca
Dx 56
A&W
Bilateral
Breast Ca
Dx 45
Dx ?
Diabetes
d. 70’s
Breast Ca
Dx 69
63
George
HTN
35
PATIENT
A&W
76
d. MI
60
Irene
A&W
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David
A&W
Ovarian
Breast Ca
Dx 72
58
Jean
↑ Chol
30
Michael
A&W
30
Jason
A&W
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Possible Genetic Testing Results
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Possible Genetic Testing Results
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Possible Genetic Testing Results
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Possible Genetic Testing Results
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What are the
benefits / harms
of genetic testing for
hereditary breast/ovarian
cancer?
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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?”
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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!”
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Benefits
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HARMS – Mutation Present
 Disease
Causing Mutation Present
Socio-legal Harms
 Insurance
 Other
premiums may be increased
Harms
Fear!
 Patient may become fatalistic towards health
 Other family members may become distressed on
patient’s or their own behalf
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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
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HARMS – Mutation Absent
 Clear
Negative gene test result
 Emotional
harm
Survivor Guilt
 Cannot identify with the disease group
 No excuse for life problems
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HARMS - Mutation Absent
 Uninformative Test
 Health
Result
Behaviour Harm
 Complacency
 Fatalism
towards health
 Still need to follow clinical recommendations as
family history risk still present
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Harms
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What can be done for BRCA Mutation Carriers to
reduce the risk of breast/ovarian cancer?
Surgical options
mastectomy
- 90% risk reduction in high-risk
women
- Bilateral risk-reducing
oophorectomy
- hazard ratio for br ca = 0.47
- hazard ratio for ovarian ca = 0.04
- Bilateral risk-reducing
Chemoprevention
-Tamoxifen
- raloxifene, aromatase
inhibitors
- shows promise in BRCA2 carriers
- under study
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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?

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Genetic Clinic Resources
 Talk
to your local genetics clinic
 Check
whether referral appropriate
 Update on new genetic tests or advancements
 Contact
information in package
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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
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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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Gene Messenger
To

suggest topics, email us at:
[email protected]
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GenetiKit Web Site
www.genetikit.com
Password: genetics
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Thank you.
Questions?
Please fill in the
workshop evaluation
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