Handbook of Genetic Counseling/Breast Cancer - Ashkenazi Jew

Breast Cancer - Ashkenazi Jew

Introduction

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

Contracting

 * 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

 * 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

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

Psychosocial
(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

 * 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?

 * 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

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

Familial chance of risk

 * 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)

 * 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

 * 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

 * 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

 * 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

 * 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