Behavioral

1
Behavioral Psychosocial Consequences of BRCA1
Mutation Testing

• Ken R. Smith

2
A Fundamental Question

• Asked of members of high-risk breast and ovarian
  cancer families
• Do you want to know whether you have a mutation
  that increases your risk of cancer?

3
Choosing to Be Tested

• Why do you want this information?
• Why dont you want this information?
• How did this information help you to prevent
  cancer?
• How did you and your family respond
  psychologically and socially?
• What have been some of the unanticipated effects
  of knowing?

4
Topics
Whether to Get Tested
Distress Following Testing
Familial Aspects of Testing
Screening/Preventive Behaviors
Life/Cancer Insurance Issues
Family Planning Decision-Making
5
Kindred 2082

• Focus is on genetic testing for a single BRCA1
  mutation in an extended kindred K2082
• K2082 identified by linking individuals
  families dispersed across the intermountain West
  using the UPDB

6
Risks of Cancer by Age 70
Increased risk of prostate colon cancer in
BRCA1 mutation carriers
7
Protocol
Identify Families
1
Informed Consent
Start
2
Baseline Interview
3
Genetic Counseling I
4
5
Blood Draw
6
DNA Testing
7
Results Offered
8
Genetic Counseling II
9
10
1 Week Interview
Finish
4m,1y,2y Interviews
8
Recommendations Made to Female Carriers

• Screening for Breast Cancer
• Monthly breast self-exam
• Clinical breast exam every 6 months gt 25
• Annual Mammogram gt25, Bi-annual gt50
• Discuss /- of prophylactic mastectomy with MD

• Screening for Ovarian Cancer
• At least annual rectovaginal pelvic exam
• CA 125 and transvaginal ultrasound
• Prophylactic bilateral oophorectomy by age 35

9
Topics
Whether to Get Tested
Distress Following Testing
Familial Aspects of Testing
Screening/Preventive Behaviors
Life/Cancer Insurance Issues
Family Planning Decision-Making
10
Percentage Choosing to be Tested for BRCA1/BRCA2
Mutations
11
Yes and KnowWho Chooses to be Tested
Clusters of participants by family
12
Reasons for Choosing to Be Tested

• Effects on children and grandchildren
• Prevention and surveillance
• Saw what cancer did to my mother
• Finding a cure wanting to help
• Family Planning
• Eliminate uncertainty
• Nuclear testing, Downwinders

13
Reasons for NOT Being Tested

• Concerns over privacy
• Insurance/employment discrimination
• Hassle of face-to-face genetic counseling
• Most non-joiners do not reveal their reasons

14
Topics
Whether to Get Tested
Distress Following Testing
Familial Aspects of Testing
Screening/Preventive Behaviors
Life/Cancer Insurance Issues
Family Planning Decision-Making
15
Is There a There There?

• Distress and anxiety following receipt of BRCA1
  mutation test results the early results
• Modest adverse psychological effects among
  mutation carriers
• Short-term follow-up

16
Anxiety (State Anxiety Scale of STAI) Before and
2 Weeks After BRCA1 Testing
Louisiana
Utah
General Anxiety
Health Psychol., 166372, 1997
17
At-Risk Subsets Among Carriers

• Differences among Carriers
• Looking beyond the short-run
• Surgeries
• Risk perception
• Family Patterns of Results

18
Measuring Distress Revised Impact of Event
Scale(Intrusion and Avoidance)

• I thought about it when I didn't mean to (I)
• I had trouble falling asleep or staying asleep,
  because of pictures or thoughts about it that
  came into my mind (I)
• I avoided letting myself get upset when I thought
  about it or was reminded of it (A)
• I tried to remove it from memory (A)
• I felt as if it hadn't happened or was not real
  (A)
• Score of 20 approximates distress experienced by
  women recently diagnosed with breast cancer

19
Gender Differences in Distress Over Time
Following BRCA1 Testing
Impact of Event Scale
20
Distress Following BRCA1 Testing and Whether Ever
Had Oophorectomy Before Testing
Impact of Event Scale
21
Distress Following BRCA1 Testing and Whether Ever
Had Oophorectomy After Testing
Impact of Event Scale
had at least one ovary at testing
22
Perceived Risks

• Before your participation in this study, did you
  know or suspect that you were part of a family
  that has a higher than normal risk for breast and
  ovarian cancer?

23
Knew or Suspected High Risk Before Testing -
Women
Impact of Event Scale
24
Topics
Whether to Get Tested
Distress Following Testing
Familial Aspects of Testing
Screening/Preventive Behaviors
Life/Cancer Insurance Issues
Family Planning Decision-Making
25
Role of Siblings and Spouses

• Similar or Different Test Results Among Siblings
• Supportive Spouse

26
Distress 2 Weeks After TestingEffects of
Sibling Test Results
Sibling Results
Impact of Event Scale
Cancer Epidem, Biomarkers Prevention, 1999 8,
385392
27
Tested Men With and WithoutCarrier Sisters
Impact of Event Scale
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Effect of Husbands Anxiety Support on Carrier
Women
Impact of Event Scale
American Journal of Medical Genetics Part C,
119C3544 (2003)
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Topics
Whether to Get Tested
Distress Following Testing
Familial Aspects of Testing
Screening/Preventive Behaviors
Life/Cancer Insurance Issues
Family Planning Decision-Making
30
Mammography Adherence for Carrier Women gt 25
years of age, K2082
American Journal of Medical Genetics 118A201209
(2003)
31
Prophylactic Oophorectomy by 2-Years Following
BRCA1 Testing K2082
American Journal of Medical Genetics 118A201209
(2003)
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Prophylactic Oophorectomy Among BRCA1/2 Mutation
Carriers
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Prophylactic Mastectomy Among BRCA1/2 Mutation
Carriers
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Topics
Whether to Get Tested
Distress Following Testing
Familial Aspects of Testing
Screening/Preventive Behaviors
Life/Cancer Insurance Issues
Family Planning Decision-Making
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Insurance Employment

• Life Insurance Discrimination
• No evidence thus far
• Employment Discrimination
• No evidence thus far

American Journal of Medical Genetics 932939
(2000)
36
Whos Going To Know? Disclosure of Test Results
Genetic Testing 2002 689-92
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Adverse Selection

• What is Adverse Selection?
• Consumers who test positive for gene mutations
  associated with serious diseases will seek high
  levels of insurance protection at premiums that
  are below actuarially justified values
• No evidence with respect to life insurance
• Less likely to see this with respect to health
  insurance

38
Cancer Insurance I

• So-called Dread Disease policies
• Covers a single disease
• Inquiries to genetic counselors by K2082 research
  subjects
• Largest cancer insurance supplier is AFLAC (Am.
  Fidelity Life Assurance Co.)

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Cancer Insurance II

• Most policies are similar to life insurance
  policies
• Paid upon proof of event (i.e., cancer diagnosis)
• Benefits given as a lump sum and/or a schedule of
  benefits for the direct costs of cancer treatment
• Policy holder has discretionary power over
  spending
• Controversial
• Low payout (NJ does not allow sale of CI)
• Fear that people will substitute CI for HI
• Numerous types of policies with many limits and
  exclusions (may be hard to compare policies)

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Cancer Insurance III

• K2082 Men and Women
• 11 have CI
• 16 are considering CI
• Members of K2082 are 2.7 times more likely to
  have CI than general public

Journal of Consumer Policy 2001241-21
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Topics
Whether to Get Tested
Distress Following Testing
Familial Aspects of Testing
Screening/Preventive Behaviors
Life/Cancer Insurance Issues
Family Planning Decision-Making
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Why Is Reproductive Decision-Making An Issue?

• Passing on risk to children
• Having dependent children see you become ill
• Fear of dying before children grow up (females)
• Identifying with/caring for affected female
  relative (females)

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Fertility Intentions
Looking to the future, do you and your
(wife/husband) intend to have a(nother) child
sometime?
Yes
How sure are you that you will have (more)
children? Are you ... Very sure, moderately
sure, or not sure at all
Very sure, moderately sure
44
Intentions to Have A(nother) Childand Genetic
Status among Women
Carrier
Non-Carrier
Months Post-Test
Cancer Epidemiol Biomarkers Prev 200413(5)733-40
45
Intentions to Have A(nother) Child at All 3
Post-Testing Interviews By Genetic Status Among
Women
Carrier
Non-Carrier
46
Intentions to Have A(nother) ChildAmong Spouses
of Tested Persons at 1 Year Interview
43
Percentage
16
16
0
47
What do you think will be the positive or
negative things that will happen to your family
and relatives because of the availability of
testing for the BRCA1 mutation?

• I'm afraid it will make some of them limit
  their families since they're worried about
  passing on the gene.
• Well my daughters are having such a problem with
  it, they decided not to have children.
• I think we've already had some that chose not to
  have further children in their family.
• I can't see any negatives other than that maybe
  some of them will get over-emotional about it.
  Some of them might not have children because of
  it.

48
Percentage of Women of Child-Bearing Age Who
Have Had Children Up to 5 Years Post-Testing
P.058 for trend, n53, Utah resident
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Summary (1 of 2)

• Who Tests
• Large fraction of people are not tested in our
  research protocol (with free counseling
  testing, extensive safeguards to ensure
  confidentiality)
• Less known about certain at-risk sub-groups
  (e.g., men in high risk families BRCA1) who do
  not test
• Test-Related Distress
• Modest effects overall
• Identified subsets of carriers and non-carriers
  who were at significantly greater risk
• Persistent elevated distress deserves more
  attention
• The long-term psychological effects are unknown

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Summary (2 of 2)

• Screening and Prevention
• Mammography non-adherence among some carriers
• Opt for oophorectomy, associated with distress
• Insurance
• Little adverse selection with respect to life
  insurance
• Emergence of cancer insurance as an issue
• Fertility
• Carriers may reduce their fertility due to
  concerns about heritability and personal health
• Early evidence that carriers want fewer children

51
Psychosocial Behavioral Issues in the Future

• Demand for testing may increase as treatment
  options and screening behaviors are tailored to
  an individuals genotype
• Demand may decrease because of continued concerns
  about discrimination stigma and limited medical
  genetics services
• Challenge of population-based testing for genetic
  variants with low penetrance associated with
  common diseases

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BRCA1 Testing Study

• PI/Co-PI
• Jeffrey R. Botkin
• Robert T. Croyle
• Ken R. Smith
• Caryn Lerman
• Oncologist
• John H. Ward
• Genetic/Family Counselors
• Bonnie J. Baty
• Jamie McDonald
• Vickie Venne
• Corinne Halls

• Project Managers
• Jean E. Wylie
• Debra Ma
• Diana Lane
• Post Docs/Grad Students
• Anna Chan
• Heidi A. Hamann
• Rob Nielsen
• Andrea Salvador
• Nan Stroup
• Jennifer West