Handbook of Genetic Counseling/Breast Cancer - Ashkenazi Jew

Breast Cancer - Ashkenazi Jew

Introduction

(throughout)

Recently diagnosed with cancer/ currently undergoing treatment. How are you dealing with all of this?
Who do you go to for support?
Many family members with cancer. How did that impact your idea of risk?
Have you talked about this appointment with your family?
Are you concerned for your own health, what are your concerns/fears?
Have you considered the implications to the rest of your family?
Have you thought about what if it wasn't familial? How will you feel if testing is not warranted?

Basic definition: the uncontrolled growth of cells.
Divisions
- 70-80% = sporadic (just happens to people for no connected reason -no previous family history)
- 20-30% = familial
chance alone
genetic susceptibility
shared environment
combination
- 5-10% = inherited - this is what we are concerned about and can help you test for
BRCA1
BRCA2
other genes?
Genes and chromosomes
- People -> genes -> nucleotides = CAGT
chromosomes = instruction manual
genes= instructions
amnio acids = words
nucleotides = letters
- Two copies of every chromosome, every gene.
- Dominant Inheritance (50%)
Cancer is actually caused by a change in a tumor suppressor gen*= they control cell growt*When both copies of the gene are changed (have a mutation) they cannot stop cell growth = tumor. (Two-hit hypothesis)
- Two different ways it can be affected
acquired
inherited
The genes
- Chromosome 17 (BRCA1)
- Chromosome 13 (BRCA2)

Background risk of BRCA1/BRCA2 mutation carrier for As*Jewish heritage
- 1/40 is a mutation carrier
Three common mutations
- BRCA1 - 185delAG (1.0%)
- BRCA1 - 5382insC (0.15%)
- BRCA2 - 617delT (1.5%)
BRCAPRO - 28.0% chance of carrying BRCA1 or BRCA2
- BRCA1 - 9.5%
- BRCA2 - 18.5%
Couch model
- avg age of dx 50-55 = 12.7% for BRCA1
Shattuck-Eidens greater than 2 br. c*greater than 51 dx = 13% for BRCA1
Claus Model (risk for your daughters to develop cancer) - based only on their mother.
- Describe the numbers using the chart with the client* (get this chart!!)
0.2% by age 29
0.8% by age 39
2.3% by age 49
4.9% by age 59
8.2% by age 69
11.0% by age 79 -lifetime risk.

Three types of risk
- population risk
- age based risk
- lifetime risk
Risks associated with dev. Breast cancer
- General pop. Lifetime = 11%
- BRCA1/BRCA2 lifetime = 87%
Jewish carriers - 56% lifetime
- BRCA1/BRCA2 age 40 = 20%
- BRCA1/BRCA2 age 59 = 59%
- BRCA1/BRCA2 age 70 = 82%
Risk of dev. Second primary breast tumor BRCA1
- age 50 = 48%
- age 70 = 64%
Risk of second breast cancer with BRCA2
- 50% lifetime risk
Ovarian cancer risk
- General pop lifetime = 1-2%
- age 50 w/ BRCA1= 29%
- age 70 w/BRCA1 = 44%
- Jew. Pop= 16%
- age 70 w/BRCA2 = 15-20%
Other cancer risks
- Prostate cancer = 30% (gen. pop = 17%)
- laryngeal cancer, pancreatic cancer = slight increase
- Jewish pop. prostate cancer=16% (depending on mutation - see results session outline)
- Colon cancer slight increase
- Male breast in BRCA2 age 70 = 6% (pop.=0.1%)

The actual test
- Ashkenazi triplet test (direct mutation analysis)
$375
- BRCA1/BRCA2 sequencing
after triplet screen = $2380
Reasons to test
- improved risk management
- answer ? about the cancer risk
- Info for family members
- Lifestyle choices
Reasons not to test
- psychological distress
- worries of discriminations of employment/insurance
- change in family dynamics
guilt complex
survivor guilt
- false sense of security
Limitations of testing
- The possible results of As*Jew. panel
positive result
negative result - may be one of the 17% who do not have the common mutations. Strong indication to do sequencing.
- the possible results of sequencing
positive, known mutation
negative result - not informative unless we know a previous mutation
mutation of unknown significance - it is a mutation but we don't know what it means.
- not all mutations are detected
- results are a probability, not a certainty.
Two types of testing
- Research
free
only tests some of the genes
detects 50% of mutations
takes 6-12 months
- Clinic
expensive ($2400 for first relative)
sequences entire gene
takes 3-6 weeks (one month)

Health insurance
- passage of HIPAA (Health insurance portability and accountability act)
for groups plans
protects from a change in individual charge based on genetic testing
genetic testing results can not be viewed as a previously existing condition
doesn't prevent access to genetic info.
doesn't prevent insurers from demanding testing as a coverage condition
doesn't prevent group rate hikes
doesn't provide protection if you are outside a group plan.
doesn't cover life or disability issues

Positive for deleterious mutation
Negative for mutation
- means that for the areas tested, there is no gene mutation.
- ONLY definitive if thee is a known mutation in the family
- Possibility of other genes that we don't know about.
Variant of unknown significance

Breast recommendations for at risk family members
- monthly self breast exam (starting at age 18)
- clinical surveillance - every 6-12 months (starting at age 25)
- annual mammography (age 25-35)
- prophylactic mastectomy
reduces risk
Ovarian screening
- Pelvic exam
- Transvaginal ultrasound -every 6-12 months (staring at age 25-35)
more sensitive than transabdominal ultrasound
minor discomfort (bladder is empty)
assess abnormal structural findings
- ovarian volume
- cyst wall thickness
- septal structure
- CA-125 testing - every 6-12 months
measures a chemical in your blood - glycoprotein antigen - shed in blood stream from ovarian cancer cells.
level is elevated ½ patients with stage I ovarian cancer
level is elevated in 90% of patients stage II ovarian cancer
sensitivity is low
specificity is low due to other contributing factors
- prophylactic oophorectomy
eliminates primary ovarian cancer risk (but residual could have cancer)
induces menopause
Colon screening
- colonoscopy every 3-5 years starting age 50
- annual fecal occult tests

The information in this outline was last updated in 2000.

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