Genetics and Ovarian Cancer June 16 2015 Ovarian

Genetics and Ovarian Cancer June 16, 2015 Ovarian Cancer Alliance of Oregon and SW Washington Becky Clark, MS, CGC Genetic Counselor

Risk for Ovarian cancer • ~20% of ovarian cancers are related to an inherited cancer syndrome • ~80% of ovarian cancers are sporadic Your relative with ovarian cancer Your risk None 1% Mother/Sister 4 -6% Grandmother/Aunt 1 -2%

Cancer development Normal cells One cell at risk Tumor develops First mutation Second mutation

Autosomal Dominant Inheritance Parents Children 50% chance of inheriting gene change 50% chance of inheriting unchanged gene

Gene mutations increasing risk for ovarian cancer • Hereditary breast and ovarian cancer syndrome • BRCA 1, BRCA 2 • Lynch syndrome • MLH 1, MSH 2, MSH 6, PMS 2, EPCAM • • • • BARD 1 BRIP 1 CDH 1 CHEK 2 MRE 11 A MUTYH NBN PALB 2 RAD 50 RAD 51 C RAD 51 D STK 11 TP 53

Goals of genetic testing • Understand cause of cancer in family • Surveillance and prevention of other cancers • Allow unaffected family members to test • Surveillance • Prevention options • Family planning

Hereditary breast and ovarian cancer syndrome: BRCA 1 and BRCA 2 Prevalence in the general population: ~1 in 400 Prevalence in the Ashkenazi Jewish population: ~ 1 in 40 Consider when history includes one of the following: • Ovarian cancer at any age • Breast cancer at or before age 50 • Triple negative breast cancer at or before age 60 • Two primary breast cancers in the same person or on the same side of family • Breast and ovarian cancer in the same person • ≥ 3 relatives with breast, ovarian, pancreatic cancer and/or aggressive prostate cancer on the same side of family • Ashkenazi Jewish Ancestry and a personal or family history of breast, ovarian or pancreatic cancer • Male breast cancer

BRCA mutation cancer risks General Population BRCA 1 or BRCA 2 mutation Breast 12% 40 -80% Ovarian 1% 11 -40% Male Breast 0. 1% 1 -10% Prostate 15 -18% <30 -39% Pancreatic 0. 5% 1 -7% Increased risk for a second primary breast cancer Reports of increased risk for melanoma

BRCA family tree

Lynch syndrome: MLH 1, MSH 2, MSH 6, PMS 2, EPCAM Consider when history includes one of the following: • Colon cancer before age 50 • Uterine cancer before age 50 • ≥ 2 Lynch cancers in the same person • ≥ 2 relatives with a Lynch cancer, one <50 years old • ≥ 3 relatives with a Lynch cancer at any age • Abnormal MSI and/or IHC tumor test result • Performed on colon and uterine tumors

Lynch syndrome cancer risks General Population Risk Lynch syndrome Colorectal 5. 5% 40 -80% Uterine 2. 7% 25 -60% Stomach <1% 1 -13% Ovarian 1. 6% 1 -24% Also at increased risk: Small intestine, biliary system (pancreas, liver, bile duct), brain, skin, and urinary tract (kidneys, ureters, bladder, urethra)

Lynch family tree

Genetic testing for ovarian cancer • Ashkenazi Jewish? Start with the three founder mutations in BRCA 1 and BRCA 2 • Testing to include BRCA 1, BRCA 2, and Lynch syndrome • Recent availability of panel tests: covers BRCA 1, BRCA 2, Lynch syndrome, and other more rare, lower risk genes • Single site testing for family members if relative tests positive

Insurance coverage • Covered benefit if medical criteria is met (NCCN criteria). Some insurance have their own criteria. • Always pre-authorized by the genetic testing lab • Out of pocket cost depends on your insurance plan • Discounted prices for those without insurance coverage

Laws that protect against genetic discrimination in health insurance and employment • HIPAA: Health Insurance Portability and Accountability Act • Federal law • GINA (Genetic Information Non-Discrimination Act) 2008 • Applies to family history and genetic test results • Does not cover life insurance, long-term disability • State laws • Oregon law DOES cover life insurance and long-term disability • Applies to genetic test results, not family history

Types of results from genetic testing • Negative: no mutation detected • Base cancer risks on family history • Positive: mutation detected that causes an increased risk for cancer • Follow management guidelines for care • Offer genetic testing to other family members • Variant of uncertain significance (VUS): • Change identified, but not enough evidence to determine if disease causing or benign • Identified in ~10% of tests • Cannot test family members. Exception: Family Studies Programs • VUS will be reclassified over time

Thinking about the future • DNA banking • Store DNA at a facility for future testing • Fertility preservation and family planning • Freezing eggs • Pre-implantation Genetic Diagnosis (PGD) • Prenatal testing (amniocentesis)

Contact Compass Oncology GREAT Program Genetic Risk Evaluation & Testing Lucy Langer, MD, MSHS Becky Clark, MS, CGC Lisa Clark, FNP, AOCNP, APNG Phone: 503 -297 -7403