# 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

## Notes

The information in this outline was last updated in 2000.