BRCA1 Mutation Test Results and Heterogeneity in PsychoSocial Outcomes

1
BRCA1 Mutation Test Results and Heterogeneity
in Psycho-Social Outcomes

• Ken R. Smith, Jeffery R. Botkin,
• Robert T. Croyle, Jean Nash, Heidi Hamann,
• Bonnie Baty, Anna Chan,
• Antoinette Stroup, Lee Ellington
• University of Utah and
• National Cancer Institute

2
Is There a There There?

• With respect to distress and anxiety
• Modest adverse psychological effects among
  mutation carriers
• Short-term follow-up

3
Focusing on Heterogeneity

• TIME INTERVAL
• Short-term vs. Longer-term follow-up
• TYPES OF CARRIERS
• Risk perception, Surgeries, Family Patterns of
  Results
• RANGE OF OUTCOMES
• Additional social outcomes beyond psychological
  distress
• Consider reproductive decision making

4
Short-Term Heterogeneity in Distress Following
Receipt of BRCA1 Test Results

• Past analysis showed that 1-2 weeks
  post-testing
• Unaffected female mutation carriers with no
  cancer or cancer-related surgery had highest
  levels of test-related distress (IES)
• Among siblings, the first/only mutation carrier
  encountered the highest levels of test-related
  distress (IES)

5
Longer-Term Heterogeneity in Distress

• Distinguish between immediate (1-2 weeks) and
  subsequent (4-24 months) effects on distress
• Analyze growth curves using HLM

A
Possible Carrier Distress Profiles
B
Distress
C
D
Non-Carriers
Time
6
Reproductive Decision Making
Possible Concerns of Carriers

• 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 women
  (females)

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
Kindred 2082
Links between genealogy and cancer registry,
family expansion N108 women (39 carriers) N73
men (27 carriers) Complete data on all
covariates at all 4 interviews (1wk, 4m, 1y
2y) SES Marital Status Family and Personal
Cancer History Risk Perception Surgical History
Carrier Non-Carrier
9
Test-Related Distress
Impact of Event Scale
Averaged Person-Specific Scores Across 4
Post-Test Interviews
10
Gender Differences Over Time
11
Oophorectomy Before Testing
12
Had Oophorectomy After Testing
had at least one ovary at testing
13
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?
• On a scale from 0 to 100, where 0 is no chance
  at all and100 is absolutely certain, what do you
  think are the chances that you HAVE A GENE that
  will increase your risk of BREAST CANCER?

14
Knew or Suspected High Risk Before Testing -
Women
15
Knew or Suspected High Risk Before Testing - Men
16
Tested Men With and WithoutCarrier Sisters
17
Fertility Intentions

• Looking to the future, do you and your
  (wife/husband) intend to have a(nother) child
  sometime?
• How sure are you that you will have (more)
  children? Are you ... VERY SURE, MODERATELY
  SURE, NOT AT ALL SURE
• Adjusts for parity, income, education, personal
  and family cancer history, age, marital status.

18
Intentions to Have A(nother) ChildAge 35 or
Younger
Percentage
Months Post-Test
19
Intentions to Have A(nother) ChildBy Gender
Genetic Status (35 or younger)
Carrier
Non-Carrier
Men
Women
Months Post-Test
Months Post-Test
20
Intentions to Have A(nother) ChildAmong Spouses
of Tested Persons at 1 year
43
Percentage
16
16
0
21
Attributing Changes in Fertilityto Test Results

• Have you changed your plans about how many
  children to have because you know your genetic
  status?
• Do you think that your past decisions about
  whether to have children, the number of children,
  or when you would have them, have been affected
  in any way because cancer may run in your family?

22
Changed Childbearing Because of Family Cancer
History or Test Results
Percentage
Months Post-Test
23
Summary

• Test-Related Distress
• Modest effects overall
• Identified subsets of carriers and non-carriers
  who were at greater risk
• Modest risks that persist may deserve more
  attention
• Fertility
• Carriers may reduce their fertility due to
  concerns about heritability and personal health
• Intentions (often) translate into behavior