Handbook of Genetic Counseling/Breast Cancer - Ashkenazi Jew

From Wikibooks, open books for an open world
< Handbook of Genetic Counseling
Jump to: navigation, search

Breast Cancer - Ashkenazi Jew

Introduction[edit]

  • How are they, did they have any problems finding the place?

Contracting[edit]

  • Find out what she knows about cancer and testing.
  • Review family history
  • Review medical history
  • What cancer is, how it happens
  • Talk about the specific risks to your family
  • Talk about the testing options and what it can tell you.
  • Talk about management

Family history[edit]

  • Names of relatives
  • Cousins?
  • Daughters' screening practices?
  • Any more details about age of living uncles (paternal and maternal)
  • Bilateral/unilateral cancers?
  • Any idea about country paternal great-grandmother is from?
  • Anyone else with cancer?
  • Could we get documentation of the sarcoma or brain tumors?
  • Any leukemias?
  • Any pancreatic, melanoma?

Medical history[edit]

  • How is she doing currently?
  • What are current screening practices? mammograms, self exams?
  • Any surgeries?
  • Any hospitalizations?
  • Medications?
  • Exercise/diet?

Psychosocial[edit]

(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?

Causes of breast cancer[edit]

  • 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)

Who do we offer testing for - at greater risk?[edit]

  • More than one family member with cancer*
  • Single woman with breast and ovarian
  • Woman with bilateral breast cancer
  • Early onset age of cancer (<50)
  • Ovarian cancer at any age
  • Ashkenazi Jewish*
  • Odd cancers - male breast cancer, laryngeal cancer

Based on your family history[edit]

  • What do you think you risk of being a carrier is?

Familial chance of risk[edit]

  • 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.

Cancer risks (for carriers of BRCA1/2)[edit]

  • 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%)

Testing[edit]

  • 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)

Discrimination Issues[edit]

  • 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

Results[edit]

  • 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

Management[edit]

  • 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

Notes[edit]

The information in this outline was last updated in 2000.