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

2. 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 None1% Mother/Sister4-6% Grandmother/Aunt1-2%

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

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

7. Gene mutations increasing risk for ovarian cancer Hereditary breast and ovarian cancer syndrome BRCA1, BRCA2 Lynch syndrome MLH1, MSH2, MSH6, PMS2, EPCAM BARD1 BRIP1 CDH1 CHEK2 MRE11A MUTYH NBN PALB2 RAD50 RAD51C RAD51D STK11 TP53

8. 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

9. Hereditary breast and ovarian cancer syndrome: BRCA1 and BRCA2 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

10. BRCA mutation cancer risks General PopulationBRCA1 or BRCA2 mutation Breast12%40-80% Ovarian1%11-40% Male Breast0.1%1-10% Prostate15-18%<30-39% Pancreatic0.5%1-7% Increased risk for a second primary breast cancer Reports of increased risk for melanoma

11. BRCA family tree

12. Lynch syndrome: MLH1, MSH2, MSH6, PMS2, 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

13. Lynch syndrome cancer risks General Population RiskLynch syndrome Colorectal5.5%40-80% Uterine2.7%25-60% Stomach<1%1-13% Ovarian1.6%1-24% Also at increased risk: Small intestine, biliary system (pancreas, liver, bile duct), brain, skin, and urinary tract (kidneys, ureters, bladder, urethra)

14. Lynch family tree

15. Genetic testing for ovarian cancer Ashkenazi Jewish? Start with the three founder mutations in BRCA1 and BRCA2 Testing to include BRCA1, BRCA2, and Lynch syndrome Recent availability of panel tests: covers BRCA1, BRCA2, Lynch syndrome, and other more rare, lower risk genes Single site testing for family members if relative tests positive

16. 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

17. 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

18. 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

19. 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)

20. 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