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.